5-150357658-T-G

Position:

• chr5-150357658-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000377797.7(TCOF1):​c.-89T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,236,910 control chromosomes in the GnomAD database, including 614,562 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (75833 hom., cov: 32)
  • Exomes 𝑓: 1.0 (538729 hom.)
• Consequence: TCOF1 ENST00000377797.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.696

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-150357658-T-G is Benign according to our data. Variant chr5-150357658-T-G is described in ClinVar as [Benign]. Clinvar id is 1258191.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150357658-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCOF1	NM_001371623.1			upstream_gene_variant		ENST00000643257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCOF1	ENST00000643257.2			upstream_gene_variant			NM_001371623.1	P3

Frequencies

GnomAD3 genomes AF: 0.998 AC: 151854 AN: 152160 Hom.: 75774 Cov.: 32

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.998

GnomAD4 exome AF: 0.997 AC: 1081040 AN: 1084632 Hom.: 538729 Cov.: 14 AF XY: 0.997 AC XY: 544095 AN XY: 545890

Gnomad4 AFR exome AF: 0.999

Gnomad4 AMR exome AF: 0.999

Gnomad4 ASJ exome AF: 0.997

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.996

Gnomad4 OTH exome AF: 0.998

GnomAD4 genome AF: 0.998 AC: 151972 AN: 152278 Hom.: 75833 Cov.: 32 AF XY: 0.998 AC XY: 74333 AN XY: 74466

Gnomad4 AFR AF: 0.999

Gnomad4 AMR AF: 1.00

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.998

Alfa AF: 0.997 Hom.: 9202

Bravo AF: 0.998

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4565199; hg19: chr5-149737221;