5-150376282-A-G

Variant names:

• chr5-150376282-A-G
• rs34796297
• NM_001371623.1:c.2094A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001371623.1(TCOF1):​c.2094A>G​(p.Glu698Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,614,126 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (101 hom., cov: 34)
  • Exomes 𝑓: 0.0020 (99 hom.)
• Consequence: TCOF1 NM_001371623.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.438
• Publications: 3 publications found

Genes affected

TCOF1 (HGNC:11654): (treacle ribosome biogenesis factor 1) This gene encodes a nucleolar protein with a LIS1 homology domain. The protein is involved in ribosomal DNA gene transcription through its interaction with upstream binding factor (UBF). Mutations in this gene have been associated with Treacher Collins syndrome, a disorder which includes abnormal craniofacial development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

TCOF1 Gene-Disease associations (from GenCC):

• Treacher Collins syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Treacher-Collins syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 5-150376282-A-G is Benign according to our data. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150376282-A-G is described in CliVar as Benign. Clinvar id is 130567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.438 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCOF1	NM_001371623.1	c.2094A>G	p.Glu698Glu	synonymous_variant	Exon 13 of 27	ENST00000643257.2	NP_001358552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCOF1	ENST00000643257.2	c.2094A>G	p.Glu698Glu	synonymous_variant	Exon 13 of 27		NM_001371623.1	ENSP00000493815.1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3050 AN: 152148 Hom.: 103 Cov.: 34

Gnomad AFR AF: 0.0695

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00837

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.00509 AC: 1271 AN: 249858 AF XY: 0.00384

Gnomad AFR exome AF: 0.0720

Gnomad AMR exome AF: 0.00344

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00204 AC: 2986 AN: 1461860 Hom.: 99 Cov.: 34 AF XY: 0.00173 AC XY: 1255 AN XY: 727232

African (AFR) AF: 0.0717 AC: 2399 AN: 33478

American (AMR) AF: 0.00398 AC: 178 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5764

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1111998

Other (OTH) AF: 0.00532 AC: 321 AN: 60394

GnomAD4 genome AF: 0.0200 AC: 3047 AN: 152266 Hom.: 101 Cov.: 34 AF XY: 0.0187 AC XY: 1396 AN XY: 74458

African (AFR) AF: 0.0692 AC: 2876 AN: 41550

American (AMR) AF: 0.00836 AC: 128 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68004

Other (OTH) AF: 0.0142 AC: 30 AN: 2116

Alfa AF: 0.0106 Hom.: 25

Bravo AF: 0.0230

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jan 25, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Treacher Collins syndrome 1 Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.0
DANN	Benign	0.55
PhyloP100		-0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34796297; hg19: chr5-149755845;