10-12160939-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018144.4(SEC61A2):​c.985G>A​(p.Gly329Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SEC61A2
NM_018144.4 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.11664623).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEC61A2NM_018144.4 linkc.985G>A p.Gly329Arg missense_variant Exon 10 of 12 ENST00000298428.14 NP_060614.2 Q9H9S3-1Q8TC24

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEC61A2ENST00000298428.14 linkc.985G>A p.Gly329Arg missense_variant Exon 10 of 12 1 NM_018144.4 ENSP00000298428.9 Q9H9S3-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249392
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134816
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1460012
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726328
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152280
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.985G>A (p.G329R) alteration is located in exon 10 (coding exon 10) of the SEC61A2 gene. This alteration results from a G to A substitution at nucleotide position 985, causing the glycine (G) at amino acid position 329 to be replaced by an arginine (R). 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
Pathogenic
0.61
BayesDel_addAF
Uncertain
0.066
T
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.060
.;T;.;T
Eigen
Benign
-0.058
Eigen_PC
Benign
0.099
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.97
D;D;D;D
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.12
T;T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
2.0
.;M;M;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.16
N;N;N;N
REVEL
Benign
0.12
Sift
Benign
0.44
T;T;T;T
Sift4G
Benign
0.35
T;T;T;T
Polyphen
0.052, 0.0020
.;B;B;.
Vest4
0.58
MutPred
0.44
.;Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);.;
MVP
0.13
MPC
1.1
ClinPred
0.61
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.10
gMVP
0.90

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: rs538832459; hg19: chr10-12202938; API