rs1385092969

Variant names:

• chr5-150357831-G-C
• rs1385092969
• NM_001371623.1:c.85G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-150357831-G-C
• chr5-150357831-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001371623.1(TCOF1):​c.85G>C​(p.Glu29Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCOF1 NM_001371623.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14
• Publications: 0 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• Treacher-Collins syndrome

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32662654).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371623.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	NM_001371623.1	MANE Select	c.85G>C	p.Glu29Gln	missense	Exon 1 of 27	NP_001358552.1	Q13428-3
	TCOF1	NM_001135243.2		c.85G>C	p.Glu29Gln	missense	Exon 1 of 27	NP_001128715.1	Q13428-1
	TCOF1	NM_001135244.2		c.85G>C	p.Glu29Gln	missense	Exon 1 of 26	NP_001128716.1	Q13428-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	ENST00000643257.2	MANE Select	c.85G>C	p.Glu29Gln	missense	Exon 1 of 27	ENSP00000493815.1	Q13428-3
	TCOF1	ENST00000504761.6	TSL:1	c.85G>C	p.Glu29Gln	missense	Exon 1 of 26	ENSP00000421655.2	Q13428-1
	TCOF1	ENST00000323668.11	TSL:1	c.85G>C	p.Glu29Gln	missense	Exon 1 of 26	ENSP00000325223.6	Q13428-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Treacher Collins syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	0.81	L
PhyloP100		3.1
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.020	D
Polyphen		0.92	P
Vest4		0.17
MutPred		0.28		Gain of MoRF binding (P = 0.022)
MVP		0.60
MPC		0.19
ClinPred		0.80	D
GERP RS		4.1
PromoterAI		0.052	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.69
gMVP		0.74
Mutation Taster		=85/15	polymorphism

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: rs1385092969; hg19: chr5-149737394;