3-53888465-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021237.5(SELENOK):c.38G>A(p.Arg13Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,610,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

SELENOK
NM_021237.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.970

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]

SELENOK links:

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=0.0057592094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOK	NM_021237.5 link	c.38G>A	p.Arg13Gln	missense_variant	Exon 2 of 5	ENST00000495461.6	NP_067060.2	Q9Y6D0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SELENOK	ENST00000495461.6 link	c.38G>A	p.Arg13Gln	missense_variant	Exon 2 of 5	1	NM_021237.5	ENSP00000418813.1	Q9Y6D0
SELENOK	ENST00000485414.1 link	n.270G>A		non_coding_transcript_exon_variant	Exon 3 of 3	5
SELENOK	ENST00000487571.1 link	n.105G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
SELENOK	ENST00000488746.1 link	n.38G>A		non_coding_transcript_exon_variant	Exon 2 of 5	3		ENSP00000417272.1	F8WAX7

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000299

AC:

AN:

247720

Hom.:

AF XY:

0.000342

AC XY:

AN XY:

134550

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.000205

AC:

299

AN:

1458336

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

155

AN XY:

725658

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00525

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000972

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.000381

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000409

Hom.:

Bravo

AF:

0.000336

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000467

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.38G>A (p.R13Q) alteration is located in exon 2 (coding exon 2) of the SELK gene. This alteration results from a G to A substitution at nucleotide position 38, causing the arginine (R) at amino acid position 13 to be replaced by a glutamine (Q). 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

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-0.011

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.056

Sift

Benign

0.28

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.047

B;.

Vest4

0.19

MVP

0.36

MPC

0.060

ClinPred

0.10

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over