rs755864777

Variant summary

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

The NM_018144.4(SEC61A2):​c.429G>A​(p.Met143Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SEC61A2
NM_018144.4 missense

Scores

4
3
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.86
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]

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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=0.25403017).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEC61A2NM_018144.4 linkc.429G>A p.Met143Ile missense_variant Exon 6 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.429G>A p.Met143Ile missense_variant Exon 6 of 12 1 NM_018144.4 ENSP00000298428.9 Q9H9S3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251456
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135904
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461460
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727092
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.13
CADD
Benign
20
DANN
Benign
0.96
DEOGEN2
Benign
0.0022
T;.;T;.;T;.
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.066
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.25
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.64
.;.;N;N;.;.
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
0.19
N;N;N;N;N;N
REVEL
Uncertain
0.31
Sift
Benign
0.57
T;T;T;T;T;T
Sift4G
Benign
0.50
T;T;T;T;T;T
Polyphen
0.0
.;.;B;B;.;.
Vest4
0.63
MutPred
0.50
Loss of disorder (P = 0.0651);.;Loss of disorder (P = 0.0651);Loss of disorder (P = 0.0651);Loss of disorder (P = 0.0651);Loss of disorder (P = 0.0651);
MVP
0.48
MPC
0.96
ClinPred
0.40
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs755864777; hg19: chr10-12191927; API