rs144170448

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018144.4(SEC61A2):ā€‹c.11A>Cā€‹(p.Lys4Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,485,640 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: š‘“ 0.000033 ( 0 hom., cov: 33)
Exomes š‘“: 0.000015 ( 0 hom. )

Consequence

SEC61A2
NM_018144.4 missense

Scores

4
10
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.88
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33477134).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEC61A2NM_018144.4 linkc.11A>C p.Lys4Thr missense_variant Exon 2 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.11A>C p.Lys4Thr missense_variant Exon 2 of 12 1 NM_018144.4 ENSP00000298428.9 Q9H9S3-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152130
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000212
AC:
5
AN:
235956
Hom.:
0
AF XY:
0.0000156
AC XY:
2
AN XY:
128268
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000334
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000366
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
20
AN:
1333392
Hom.:
0
Cov.:
20
AF XY:
0.0000164
AC XY:
11
AN XY:
669334
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.0000179
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152248
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000117
AC:
1
ExAC
AF:
0.0000412
AC:
5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.53
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.36
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.060
T;.;.;T;.;T;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D;D;D;D;D;D
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.33
T;T;T;T;T;T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Uncertain
2.8
.;M;.;M;M;.;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-3.0
D;D;D;D;D;D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0030
D;D;D;D;D;D;D
Sift4G
Uncertain
0.015
D;T;D;T;D;T;D
Polyphen
0.25, 0.22
.;.;.;B;B;.;.
Vest4
0.90
MVP
0.49
MPC
1.4
ClinPred
0.44
T
GERP RS
5.6
Varity_R
0.37
gMVP
0.94

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: rs144170448; hg19: chr10-12175243; API