10-12155823-C-A

Variant names:

• chr10-12155823-C-A
• NM_018144.4:c.508C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_018144.4(SEC61A2):​c.508C>A​(p.Gln170Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SEC61A2 NM_018144.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.88

Genes affected

SEC61A2 (HGNC:17702): (SEC61 translocon subunit alpha 2) The protein encoded by this gene has similarity to a mouse protein which suggests a role in the insertion of secretory and membrane polypeptides into the endoplasmic reticulum. It may also be required for the assembly of membrane and secretory proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 10-12155823-C-A is Benign according to our data. Variant chr10-12155823-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1255614.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC61A2	NM_018144.4	c.508C>A	p.Gln170Lys	missense_variant	Exon 7 of 12	ENST00000298428.14	NP_060614.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC61A2	ENST00000298428.14	c.508C>A	p.Gln170Lys	missense_variant	Exon 7 of 12	1	NM_018144.4	ENSP00000298428.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal dominant polycystic liver disease Benign:1

Sep 01, 2021

Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	.;T;.;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Uncertain	2.5	.;M;M;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.045, 0.038	.;B;B;.
Vest4		0.63
MutPred		0.48		.;Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);
MVP		0.52
MPC		1.1
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.83
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: chr10-12197822;