Genetic Variant SELENOV:p.Arg40Gln (chr19-39515331-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_182704.2(SELENOV):c.119G>A(p.Arg40Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,550,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

SELENOV
NM_182704.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.32

Variant links:

Genes affected

SELENOV (HGNC:30399): (selenoprotein V) This gene encodes a selenoprotein containing a selenocysteine (Sec) residue, which is encoded by the UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. This protein is specifically expressed in the testis. It belongs to the SelWTH family, which possesses a thioredoxin-like fold and a conserved CxxU (C is cysteine, U is Sec) motif, suggesting a redox function for this gene. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Apr 2017]

SELENOV 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=0.025363028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOV	NM_182704.2 link	c.119G>A	p.Arg40Gln	missense_variant	Exon 1 of 6	ENST00000335426.9	NP_874363.1	P59797
SELENOV	NM_001350809.1 link	c.119G>A	p.Arg40Gln	missense_variant	Exon 1 of 5		NP_001337738.1
SELENOV	NR_146916.2 link	n.-92G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOV	ENST00000335426.9 link	c.119G>A	p.Arg40Gln	missense_variant	Exon 1 of 6	1	NM_182704.2	ENSP00000333956.4		P59797
SELENOV	ENST00000597876.1 link	n.-115G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000337

AC:

AN:

151358

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.00142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000502

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000230

AC:

AN:

152384

Hom.:

AF XY:

0.000223

AC XY:

AN XY:

80864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00118

Gnomad NFE exome

AF:

0.000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000191

AC:

267

AN:

1399264

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

149

AN XY:

690150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.000184

Gnomad4 OTH exome

AF:

0.000224

GnomAD4 genome

AF:

0.000337

AC:

AN:

151474

Hom.:

Cov.:

AF XY:

0.000405

AC XY:

AN XY:

74064

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00142

Gnomad4 NFE

AF:

0.000502

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000579

Hom.:

Bravo

AF:

0.000147

ExAC

AF:

0.0000390

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 21, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.119G>A (p.R40Q) alteration is located in exon 1 (coding exon 1) of the SELV gene. This alteration results from a G to A substitution at nucleotide position 119, causing the arginine (R) at amino acid position 40 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

-0.63

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.5

DANN

Benign

0.95

DEOGEN2

Benign

0.014

T;.;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.0094

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

0.70

N;N;.

REVEL

Benign

0.060

Sift

Benign

0.48

T;T;.

Sift4G

Benign

0.54

T;T;T

Polyphen

0.97

D;.;.

Vest4

0.079

MVP

0.048

MPC

0.26

ClinPred

0.050

GERP RS

1.9

Varity_R

0.020

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.

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