chr1-51147482-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

3
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48
Variant links:
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]

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ACMG classification

Classification made for transcript

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
C1orf185NM_001136508.2 linkc.311C>A p.Ser104Tyr missense_variant Exon 5 of 5 ENST00000371759.7 NP_001129980.1 Q5T7R7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C1orf185ENST00000371759.7 linkc.311C>A p.Ser104Tyr missense_variant Exon 5 of 5 2 NM_001136508.2 ENSP00000360824.2 Q5T7R7
C1orf185ENST00000467127.5 linkc.128C>A p.Ser43Tyr missense_variant Exon 5 of 5 3 ENSP00000473351.1 R4GMU4
C1orf185ENST00000648827.1 linkc.274C>A p.Leu92Ile missense_variant Exon 4 of 4 ENSP00000497349.1 A0A3B3ISR6

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
LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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