Genetic Variant NM_002094.4:c.712A>G (chr16-11891126-T-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_002094.4(GSPT1):c.712A>G(p.Met238Val) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GSPT1
NM_002094.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

Publications

0 publications found

Variant links:

Genes affected

GSPT1 (HGNC:4621): (G1 to S phase transition 1) Enables translation release factor activity. Involved in regulation of translational termination. Acts upstream of or within protein methylation. Predicted to be located in cytosol. Predicted to be part of translation release factor complex. [provided by Alliance of Genome Resources, Apr 2022]

GSPT1 links:

RSL1D1-DT (HGNC:55337): (RSL1D1 divergent transcript)

RSL1D1-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.797

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002094.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSPT1	NM_002094.4	MANE Select	c.712A>G	p.Met238Val	missense	Exon 6 of 15	NP_002085.3	P15170-3
GSPT1	NM_001130006.2		c.709A>G	p.Met237Val	missense	Exon 6 of 15	NP_001123478.2	P15170-2
GSPT1	NM_001130007.2		c.298A>G	p.Met100Val	missense	Exon 6 of 15	NP_001123479.1	P15170-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSPT1	ENST00000434724.7	TSL:1 MANE Select	c.712A>G	p.Met238Val	missense	Exon 6 of 15	ENSP00000398131.2	P15170-3
GSPT1	ENST00000439887.6	TSL:1	c.709A>G	p.Met237Val	missense	Exon 6 of 15	ENSP00000408399.2	P15170-2
GSPT1	ENST00000420576.6	TSL:1	c.298A>G	p.Met100Val	missense	Exon 6 of 15	ENSP00000399539.2	P15170-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1336660

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

661666

African (AFR)

AF:

0.00

AC:

AN:

30010

American (AMR)

AF:

0.00

AC:

AN:

32678

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24556

East Asian (EAS)

AF:

0.00

AC:

AN:

35010

South Asian (SAS)

AF:

0.00

AC:

AN:

74420

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5544

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1031576

Other (OTH)

AF:

0.00

AC:

AN:

55784

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.067

MetaRNN

Pathogenic

0.80

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.4

PhyloP100

7.6

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-3.3

REVEL

Pathogenic

0.68

Sift

Uncertain

0.024

Sift4G

Uncertain

0.019

Polyphen

0.97

Vest4

0.54

MutPred

0.56

Gain of catalytic residue at M100 (P = 0.025)

MVP

0.87

MPC

1.5

ClinPred

0.96

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.56

gMVP

0.93

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over