3-53885842-C-A

Variant summary

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

The NM_021237.5(SELENOK):​c.265G>T​(p.Ala89Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00015 in 1,591,274 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 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

SELENOK
NM_021237.5 missense

Scores

5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09
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 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=0.12927067).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SELENOKNM_021237.5 linkc.265G>T p.Ala89Ser missense_variant Exon 4 of 5 ENST00000495461.6 NP_067060.2 Q9Y6D0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SELENOKENST00000495461.6 linkc.265G>T p.Ala89Ser missense_variant Exon 4 of 5 1 NM_021237.5 ENSP00000418813.1 Q9Y6D0
SELENOKENST00000488746.1 linkn.*38G>T non_coding_transcript_exon_variant Exon 4 of 5 3 ENSP00000417272.1 F8WAX7
SELENOKENST00000488746.1 linkn.*38G>T 3_prime_UTR_variant Exon 4 of 5 3 ENSP00000417272.1 F8WAX7

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152174
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000200
AC:
43
AN:
215432
Hom.:
0
AF XY:
0.000198
AC XY:
23
AN XY:
115926
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000957
Gnomad ASJ exome
AF:
0.000108
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000268
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000330
Gnomad OTH exome
AF:
0.000185
GnomAD4 exome
AF:
0.000157
AC:
226
AN:
1439100
Hom.:
0
Cov.:
30
AF XY:
0.000174
AC XY:
124
AN XY:
713556
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.0000953
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000243
Gnomad4 FIN exome
AF:
0.0000191
Gnomad4 NFE exome
AF:
0.000167
Gnomad4 OTH exome
AF:
0.000168
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152174
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000344
Hom.:
0
Bravo
AF:
0.000110
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000488
AC:
4
ExAC
AF:
0.000207
AC:
25

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 28, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.265G>T (p.A89S) alteration is located in exon 4 (coding exon 4) of the SELK gene. This alteration results from a G to T substitution at nucleotide position 265, causing the alanine (A) at amino acid position 89 to be replaced by a serine (S). 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
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-0.67
T
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.56
N;N
REVEL
Benign
0.11
Sift
Benign
0.074
T;T
Sift4G
Benign
0.13
T;T
Polyphen
0.99
D;.
Vest4
0.43
MVP
0.58
MPC
0.34
ClinPred
0.46
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.26

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: rs202126540; hg19: chr3-53919869; COSMIC: COSV59830984; COSMIC: COSV59830984; API