chr3-53888462-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_021237.5(SELENOK):​c.41G>A​(p.Ser14Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,611,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SELENOK
NM_021237.5 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0950
Variant links:
Genes affected
SELENOK (HGNC:30394): (selenoprotein K) The protein encoded by this gene belongs to the selenoprotein K family. It is a transmembrane protein that is localized in the endoplasmic reticulum (ER), and is involved in ER-associated degradation (ERAD) of misfolded, glycosylated proteins. It also has a role in the protection of cells from ER stress-induced apoptosis. Knockout studies in mice show the importance of this gene in promoting Ca(2+) flux in immune cells and mounting effective immune response. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Pseudogenes of this locus have been identified on chromosomes 6 and 19.[provided by RefSeq, Aug 2017]

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=0.10133374).
BP6
Variant 3-53888462-C-T is Benign according to our data. Variant chr3-53888462-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3159522.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SELENOKNM_021237.5 linkc.41G>A p.Ser14Asn missense_variant Exon 2 of 5 ENST00000495461.6 NP_067060.2 Q9Y6D0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SELENOKENST00000495461.6 linkc.41G>A p.Ser14Asn missense_variant Exon 2 of 5 1 NM_021237.5 ENSP00000418813.1 Q9Y6D0
SELENOKENST00000485414.1 linkn.273G>A non_coding_transcript_exon_variant Exon 3 of 3 5
SELENOKENST00000487571.1 linkn.108G>A non_coding_transcript_exon_variant Exon 2 of 2 2
SELENOKENST00000488746.1 linkn.41G>A non_coding_transcript_exon_variant Exon 2 of 5 3 ENSP00000417272.1 F8WAX7

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
247884
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134632
show subpopulations
Gnomad AFR exome
AF:
0.0000641
Gnomad AMR exome
AF:
0.0000580
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000480
AC:
7
AN:
1458948
Hom.:
0
Cov.:
29
AF XY:
0.00000276
AC XY:
2
AN XY:
725940
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152220
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000106

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 08, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
14
DANN
Benign
0.91
DEOGEN2
Benign
0.011
T;.
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.38
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.66
T;T
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.32
N;N
REVEL
Benign
0.11
Sift
Benign
0.24
T;T
Sift4G
Benign
0.16
T;T
Polyphen
0.0
B;.
Vest4
0.20
MutPred
0.15
Loss of disorder (P = 0.0685);Loss of disorder (P = 0.0685);
MVP
0.18
MPC
0.051
ClinPred
0.29
T
GERP RS
1.4
Varity_R
0.035

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: rs922687230; hg19: chr3-53922489; API