Variant X-51743694-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018094.5(GSPT2):c.68C>T(p.Pro23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,207,226 control chromosomes in the GnomAD database, including 22 homozygotes. There are 629 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P23T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.010 ( 9 hom., 319 hem., cov: 23)

Exomes 𝑓: 0.0011 ( 13 hom. 310 hem. )

Consequence

GSPT2
NM_018094.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.02

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038937628).

BP6

Variant X-51743694-C-T is Benign according to our data. Variant chrX-51743694-C-T is described in ClinVar as [Benign]. Clinvar id is 790238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-51743694-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1178/112543) while in subpopulation AFR AF= 0.0364 (1132/31083). AF 95% confidence interval is 0.0347. There are 9 homozygotes in gnomad4. There are 319 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSPT2	NM_018094.5 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	1/1	ENST00000340438.6	NP_060564.2	Q8IYD1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSPT2	ENST00000340438.6 linkuse as main transcript	c.68C>T	p.Pro23Leu	missense_variant	1/1	6	NM_018094.5	ENSP00000341247.4		Q8IYD1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1179

AN:

112490

Hom.:

Cov.:

AF XY:

0.00915

AC XY:

317

AN XY:

34658

show subpopulations

Gnomad AFR

AF:

0.0365

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00113

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000381

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000563

Gnomad OTH

AF:

0.00531

GnomAD3 exomes

AF:

0.00308

AC:

548

AN:

177707

Hom.:

AF XY:

0.00212

AC XY:

135

AN XY:

63713

show subpopulations

Gnomad AFR exome

AF:

0.0369

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.000979

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000882

Gnomad OTH exome

AF:

0.00138

GnomAD4 exome

AF:

0.00107

AC:

1172

AN:

1094683

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

310

AN XY:

360653

show subpopulations

Gnomad4 AFR exome

AF:

0.0345

Gnomad4 AMR exome

AF:

0.00254

Gnomad4 ASJ exome

AF:

0.000623

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000524

Gnomad4 OTH exome

AF:

0.00253

GnomAD4 genome

AF:

0.0105

AC:

1178

AN:

112543

Hom.:

Cov.:

AF XY:

0.00919

AC XY:

319

AN XY:

34721

show subpopulations

Gnomad4 AFR

AF:

0.0364

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00113

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000382

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000563

Gnomad4 OTH

AF:

0.00524

Alfa

AF:

0.000668

Hom.:

Bravo

AF:

0.0117

ESP6500AA

AF:

0.0284

AC:

109

ESP6500EA

AF:

0.000298

AC:

ExAC

AF:

0.00335

AC:

406

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.4

REVEL

Benign

0.022

Sift

Uncertain

0.025

Sift4G

Uncertain

0.023

Polyphen

0.091

Vest4

0.12

MVP

0.12

MPC

0.85

ClinPred

0.0035

GERP RS

2.7

Varity_R

0.047

gMVP

0.15

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