Variant X-51743896-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018094.5(GSPT2):c.270T>G(p.Asp90Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000573 in 1,203,950 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 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 0.000045 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.000059 ( 0 hom. 22 hem. )

Consequence

GSPT2
NM_018094.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.971

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015038073).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSPT2	NM_018094.5 linkuse as main transcript	c.270T>G	p.Asp90Glu	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.270T>G	p.Asp90Glu	missense_variant	1/1		NM_018094.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0000445

AC:

AN:

112263

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

34471

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00113

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

164723

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

53299

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000383

Gnomad ASJ exome

AF:

0.00200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000278

Gnomad OTH exome

AF:

0.000483

GnomAD4 exome

AF:

0.0000586

AC:

AN:

1091687

Hom.:

Cov.:

AF XY:

0.0000614

AC XY:

AN XY:

358015

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000289

Gnomad4 ASJ exome

AF:

0.00234

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000119

Gnomad4 OTH exome

AF:

0.000175

GnomAD4 genome

AF:

0.0000445

AC:

AN:

112263

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

34471

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00113

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000240

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000826

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

Apr 07, 2022

The c.270T>G (p.D90E) 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 270, causing the aspartic acid (D) at amino acid position 90 to be replaced by a glutamic acid (E). 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

0.062

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.036

DANN

Benign

0.50

DEOGEN2

Benign

0.016

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.25

M_CAP

Benign

0.0077

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.30

REVEL

Benign

0.015

Sift

Benign

0.18

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.062

MutPred

0.11

Gain of phosphorylation at S88 (P = 0.1921);

MVP

0.30

MPC

0.77

ClinPred

0.036

GERP RS

-6.0

Varity_R

0.067

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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