Variant chrX-51744836-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018094.5(GSPT2):c.1210T>G(p.Phe404Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,207,003 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 3 hem. )

Consequence

GSPT2
NM_018094.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.581

Variant links:

Genes affected

GSPT2 (HGNC:4622): (G1 to S phase transition 2) This gene encodes a GTPase that belongs to the GTP-binding elongation factor family. The encoded protein is a polypeptide release factor that complexes with eukaryotic peptide chain release factor 1 to mediate translation termination. This protein may also be involved in mRNA stability.[provided by RefSeq, Mar 2010]

GSPT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.076639175).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSPT2	NM_018094.5 linkuse as main transcript	c.1210T>G	p.Phe404Val	missense_variant	1/1	ENST00000340438.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSPT2	ENST00000340438.6 linkuse as main transcript	c.1210T>G	p.Phe404Val	missense_variant	1/1		NM_018094.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111781

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33935

show subpopulations

Gnomad AFR

AF:

0.0000326

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183393

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67867

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000457

AC:

AN:

1095222

Hom.:

Cov.:

AF XY:

0.00000832

AC XY:

AN XY:

360638

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:

0.00000477

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111781

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33935

show subpopulations

Gnomad4 AFR

AF:

0.0000326

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Feb 22, 2023

The c.1210T>G (p.F404V) alteration is located in exon 1 (coding exon 1) of the GSPT2 gene. This alteration results from a T to G substitution at nucleotide position 1210, causing the phenylalanine (F) at amino acid position 404 to be replaced by a valine (V). 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

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.015

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0066

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.9

MutationTaster

Benign

0.89

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.77

REVEL

Benign

0.046

Sift

Benign

0.97

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.21

MutPred

0.53

Loss of ubiquitination at K399 (P = 0.1037);

MVP

0.49

MPC

1.1

ClinPred

0.022

GERP RS

0.94

Varity_R

0.092

gMVP

0.92

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