X-51745085-C-T

Position:

• chrX-51745085-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018094.5(GSPT2):​c.1459C>T​(p.Pro487Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 23)
• Consequence: GSPT2 NM_018094.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.61

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41036955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSPT2	NM_018094.5	c.1459C>T	p.Pro487Ser	missense_variant	1/1	ENST00000340438.6	NP_060564.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSPT2	ENST00000340438.6	c.1459C>T	p.Pro487Ser	missense_variant	1/1	6	NM_018094.5	ENSP00000341247.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.1459C>T (p.P487S) alteration is located in exon 1 (coding exon 1) of the GSPT2 gene. This alteration results from a C to T substitution at nucleotide position 1459, causing the proline (P) at amino acid position 487 to be replaced by a serine (S). 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	0.31
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.053	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.64	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.20
Sift	Benign	0.33	T
Sift4G	Benign	0.76	T
Polyphen		0.66	P
Vest4		0.46
MutPred		0.50		Gain of glycosylation at P487 (P = 0.0155);
MVP		0.59
MPC		1.1
ClinPred		0.86	D
GERP RS		4.5
Varity_R		0.40
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-51488181;