chr1-51147482-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 10/15 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
• Publications: 0 publications found

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

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=0.36531943).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136508.2. 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
	C1orf185	NM_001136508.2	MANE Select	c.311C>A	p.Ser104Tyr	missense	Exon 5 of 5	NP_001129980.1	Q5T7R7
	C1orf185	NM_001410790.1		c.274C>A	p.Leu92Ile	missense	Exon 4 of 4	NP_001397719.1	A0A3B3ISR6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1orf185	ENST00000371759.7	TSL:2 MANE Select	c.311C>A	p.Ser104Tyr	missense	Exon 5 of 5	ENSP00000360824.2	Q5T7R7
	C1orf185	ENST00000467127.5	TSL:3	c.128C>A	p.Ser43Tyr	missense	Exon 5 of 5	ENSP00000473351.1	R4GMU4
	C1orf185	ENST00000648827.1		c.274C>A	p.Leu92Ile	missense	Exon 4 of 4	ENSP00000497349.1	A0A3B3ISR6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		3.5
ClinPred		0.95	D
GERP RS		4.9
Varity_R		0.30
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

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