Genetic Variant SEPHS2:p.Gly107Asp (chr16-30445408-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012248.4(SEPHS2):c.320G>A(p.Gly107Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,593,250 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G107A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 4 hom. )

Consequence

SEPHS2
NM_012248.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.732

Variant links:

Genes affected

SEPHS2 (HGNC:19686): (selenophosphate synthetase 2) This gene encodes an enzyme that catalyzes the production of monoselenophosphate (MSP) from selenide and ATP. MSP is the selenium donor required for synthesis of selenocysteine (Sec), which is co-translationally incorporated into selenoproteins at in-frame UGA codons that normally signal 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 itself a selenoprotein containing a Sec residue at its active site, suggesting the existence of an autoregulatory mechanism. It is preferentially expressed in tissues implicated in the synthesis of selenoproteins and in sites of blood cell development. A pseudogene for this locus has been identified on chromosome 5. [provided by RefSeq, May 2017]

SEPHS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048159957).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPHS2	NM_012248.4 link	c.320G>A	p.Gly107Asp	missense_variant	Exon 1 of 1	ENST00000478753.5	NP_036380.2	Q99611

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPHS2	ENST00000478753.5 link	c.320G>A	p.Gly107Asp	missense_variant	Exon 1 of 1	6	NM_012248.4	ENSP00000418669.3		Q99611

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

270

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000506

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00268

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00217

AC:

453

AN:

208516

Hom.:

AF XY:

0.00209

AC XY:

240

AN XY:

115032

show subpopulations

Gnomad AFR exome

AF:

0.000417

Gnomad AMR exome

AF:

0.000877

Gnomad ASJ exome

AF:

0.00344

Gnomad EAS exome

AF:

0.000191

Gnomad SAS exome

AF:

0.00139

Gnomad FIN exome

AF:

0.00287

Gnomad NFE exome

AF:

0.00320

Gnomad OTH exome

AF:

0.00169

GnomAD4 exome

AF:

0.00239

AC:

3440

AN:

1440886

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

1686

AN XY:

716000

show subpopulations

Gnomad4 AFR exome

AF:

0.000603

Gnomad4 AMR exome

AF:

0.000933

Gnomad4 ASJ exome

AF:

0.00359

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.00241

Gnomad4 NFE exome

AF:

0.00267

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00177

AC:

270

AN:

152364

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00268

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00160

Hom.:

Bravo

AF:

0.00197

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000272

AC:

ESP6500EA

AF:

0.00294

AC:

ExAC

AF:

0.00206

AC:

247

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Benign

1.2

DANN

Benign

0.54

DEOGEN2

Benign

0.0062

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.31

M_CAP

Benign

0.0060

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.45

PROVEAN

Benign

0.12

REVEL

Benign

0.28

Sift

Benign

0.11

Sift4G

Benign

0.62

Polyphen

0.0010

MVP

0.13

ClinPred

0.0028

GERP RS

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.045

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over