Variant 16-30445675-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012248.4(SEPHS2):c.53A>G(p.Glu18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000521 in 1,536,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

SEPHS2
NM_012248.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

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:

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=0.08609131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPHS2	NM_012248.4 linkuse as main transcript	c.53A>G	p.Glu18Gly	missense_variant	1/1	ENST00000478753.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPHS2	ENST00000478753.5 linkuse as main transcript	c.53A>G	p.Glu18Gly	missense_variant	1/1		NM_012248.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000506

AC:

AN:

1384362

Hom.:

Cov.:

AF XY:

0.00000732

AC XY:

AN XY:

683044

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000464

Gnomad4 OTH exome

AF:

0.0000347

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2023

The c.53A>G (p.E18G) alteration is located in exon 1 (coding exon 1) of the SEPHS2 gene. This alteration results from a A to G substitution at nucleotide position 53, causing the glutamic acid (E) at amino acid position 18 to be replaced by a glycine (G). 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

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0087

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.28

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.086

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.76

REVEL

Benign

0.11

Sift

Uncertain

0.0040

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.095

MutPred

0.12

Gain of loop (P = 0.0166);

MVP

0.39

ClinPred

0.25

GERP RS

2.8

Varity_R

0.11

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