3-169982799-C-A

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

19

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

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
SEC62NM_003262.4 linkc.344C>A p.Ala115Asp missense_variant Exon 4 of 8 ENST00000337002.9 NP_003253.1 Q99442
SEC62XM_011513114.4 linkc.230C>A p.Ala77Asp missense_variant Exon 5 of 9 XP_011511416.1 D3DNQ1
SEC62XM_047448819.1 linkc.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
SEC62ENST00000337002.9 linkc.344C>A p.Ala115Asp missense_variant Exon 4 of 8 1 NM_003262.4 ENSP00000337688.4 Q99442

Frequencies

GnomAD3 genomes
AF:
0.0000446
AC:
6
AN:
134594
Hom.:
0
Cov.:
32
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:
64
AN:
1407710
Hom.:
0
Cov.:
31
AF XY:
0.0000500
AC XY:
35
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:
6
AN:
134594
Hom.:
0
Cov.:
32
AF XY:
0.0000154
AC XY:
1
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.:
0
ExAC
AF:
0.00000826
AC:
1

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
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
14
DANN
Benign
0.66
DEOGEN2
Benign
0.016
T;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.71
.;T
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.038
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N
PrimateAI
Benign
0.40
T
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
T
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.

Other links and lift over

dbSNP: rs753355540; hg19: chr3-169700587; API