chr1-51147482-C-A

Variant names:

• chr1-51147482-C-A
• rs750808919
• NM_001136508.2:c.311C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001136508.2(C1orf185):​c.311C>A​(p.Ser104Tyr) 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. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C1orf185 NM_001136508.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48

Genes affected

C1orf185 (HGNC:28096): (chromosome 1 open reading frame 185) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36531943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1orf185	NM_001136508.2	c.311C>A	p.Ser104Tyr	missense_variant	Exon 5 of 5	ENST00000371759.7	NP_001129980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf185	ENST00000371759.7	c.311C>A	p.Ser104Tyr	missense_variant	Exon 5 of 5	2	NM_001136508.2	ENSP00000360824.2
C1orf185	ENST00000467127.5	c.128C>A	p.Ser43Tyr	missense_variant	Exon 5 of 5	3		ENSP00000473351.1
C1orf185	ENST00000648827.1	c.274C>A	p.Leu92Ile	missense_variant	Exon 4 of 4			ENSP00000497349.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.311C>A (p.S104Y) alteration is located in exon 5 (coding exon 5) of the C1orf185 gene. This alteration results from a C to A substitution at nucleotide position 311, causing the serine (S) at amino acid position 104 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.37	T
ClinPred		0.95	D
GERP RS		4.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs750808919; hg19: chr1-51613154; COSMIC: COSV100874466;