chr1-51147685-G-C

Position:

• chr1-51147685-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136508.2(C1orf185):​c.514G>C​(p.Glu172Gln) 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. 13/18 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: 2.94

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17050797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1orf185	NM_001136508.2	c.514G>C	p.Glu172Gln	missense_variant	5/5	ENST00000371759.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1orf185	ENST00000371759.7	c.514G>C	p.Glu172Gln	missense_variant	5/5	2	NM_001136508.2	P1
C1orf185	ENST00000467127.5	c.331G>C	p.Glu111Gln	missense_variant	5/5	3
C1orf185	ENST00000648827.1	c.*114G>C		3_prime_UTR_variant	4/4

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2021

The c.514G>C (p.E172Q) alteration is located in exon 5 (coding exon 5) of the C1orf185 gene. This alteration results from a G to C substitution at nucleotide position 514, causing the glutamic acid (E) at amino acid position 172 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.099	T;.;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.97	L;.;.
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-1.9	N;.;.
REVEL	Benign	0.058
Sift	Uncertain	0.014	D;.;.
Sift4G	Uncertain	0.053	T;D;T
Polyphen		0.068	B;.;.
Vest4		0.18
MutPred		0.12		Loss of phosphorylation at S169 (P = 0.0887);.;.;
MVP		0.61
ClinPred		0.32	T
GERP RS		4.2
Varity_R		0.10
gMVP		0.26

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-51613357;