X-51744647-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_018094.5(GSPT2):​c.1021G>A​(p.Val341Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,181 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

GSPT2
NM_018094.5 missense

Scores

3
5
9

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.62
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.871
PP5
Variant X-51744647-G-A is Pathogenic according to our data. Variant chrX-51744647-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 375379.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-51744647-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GSPT2NM_018094.5 linkuse as main transcriptc.1021G>A p.Val341Ile missense_variant 1/1 ENST00000340438.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GSPT2ENST00000340438.6 linkuse as main transcriptc.1021G>A p.Val341Ile missense_variant 1/1 NM_018094.5 P1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000182
AC:
2
AN:
1097181
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
362539
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:
0.00000238
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autism;C0036572:Seizure;C0454644:Delayed speech and language development Pathogenic:1
Pathogenic, no assertion criteria providedresearchLupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine-This variant has been identified in an individual with autism spectrum disorder, speech delay, seizures. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.0096
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.086
T
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Pathogenic
0.58
D
MetaRNN
Pathogenic
0.87
D
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Benign
0.94
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.99
N
REVEL
Uncertain
0.47
Sift
Benign
0.070
T
Sift4G
Benign
0.064
T
Polyphen
1.0
D
Vest4
0.41
MutPred
0.85
Gain of methylation at K337 (P = 0.1191);
MVP
0.86
MPC
1.5
ClinPred
0.97
D
GERP RS
4.5
Varity_R
0.42
gMVP
0.89

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.

Other links and lift over

dbSNP: rs1057519440; hg19: chrX-51487743; API