3-169982799-C-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003262.4(SEC62):c.344C>A(p.Ala115Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 134,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SEC62
NM_003262.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.854

Variant links:

Genes affected

SEC62 (HGNC:11846): (SEC62 homolog, preprotein translocation factor) The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. The protein encoded by this gene and SEC63 protein are found to be associated with ribosome-free SEC61 complex. It is speculated that Sec61-Sec62-Sec63 may perform post-translational protein translocation into the ER. The Sec61-Sec62-Sec63 complex might also perform the backward transport of ER proteins that are subject to the ubiquitin-proteasome-dependent degradation pathway. The encoded protein is an integral membrane protein located in the rough ER. [provided by RefSeq, Jul 2008]

SEC62 links:

SEC62-AS1 (HGNC:40586): (SEC62 antisense RNA 1)

SEC62-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038137883).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC62	NM_003262.4 link	c.344C>A	p.Ala115Asp	missense_variant	Exon 4 of 8	ENST00000337002.9	NP_003253.1	Q99442
SEC62	XM_011513114.4 link	c.230C>A	p.Ala77Asp	missense_variant	Exon 5 of 9		XP_011511416.1	D3DNQ1
SEC62	XM_047448819.1 link	c.230C>A	p.Ala77Asp	missense_variant	Exon 5 of 9		XP_047304775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC62	ENST00000337002.9 link	c.344C>A	p.Ala115Asp	missense_variant	Exon 4 of 8	1	NM_003262.4	ENSP00000337688.4		Q99442

Frequencies

GnomAD3 genomes

AF:

0.0000446

AC:

AN:

134594

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000829

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000489

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000455

AC:

AN:

1407710

Hom.:

Cov.:

AF XY:

0.0000500

AC XY:

AN XY:

699322

show subpopulations

Gnomad4 AFR exome

AF:

0.000129

Gnomad4 AMR exome

AF:

0.0000484

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000545

Gnomad4 SAS exome

AF:

0.0000908

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000407

Gnomad4 OTH exome

AF:

0.0000692

GnomAD4 genome

AF:

0.0000446

AC:

AN:

134594

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

64918

show subpopulations

Gnomad4 AFR

AF:

0.0000829

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000489

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000308

Hom.:

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.344C>A (p.A115D) alteration is located in exon 4 (coding exon 4) of the SEC62 gene. This alteration results from a C to A substitution at nucleotide position 344, causing the alanine (A) at amino acid position 115 to be replaced by an aspartic acid (D). 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

0.30

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.71

.;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.045

Sift

Benign

0.60

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.025

B;B

Vest4

0.24

MutPred

0.34

Loss of MoRF binding (P = 0.0502);Loss of MoRF binding (P = 0.0502);

MVP

0.20

MPC

1.6

ClinPred

0.026

GERP RS

2.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.067

gMVP

0.079

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over