NM_002094.4:c.1595A>G

Variant names:

• chr16-11877414-T-C
• rs774096473
• NM_002094.4:c.1595A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002094.4(GSPT1):​c.1595A>G​(p.Asp532Gly) 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)
• Consequence: GSPT1 NM_002094.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.64
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSPT1	NM_002094.4	MANE Select	c.1595A>G	p.Asp532Gly	missense	Exon 12 of 15	NP_002085.3	P15170-3
	GSPT1	NM_001130006.2		c.1592A>G	p.Asp531Gly	missense	Exon 12 of 15	NP_001123478.2	P15170-2
	GSPT1	NM_001130007.2		c.1181A>G	p.Asp394Gly	missense	Exon 12 of 15	NP_001123479.1	P15170-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSPT1	ENST00000434724.7	TSL:1 MANE Select	c.1595A>G	p.Asp532Gly	missense	Exon 12 of 15	ENSP00000398131.2	P15170-3
	GSPT1	ENST00000439887.6	TSL:1	c.1592A>G	p.Asp531Gly	missense	Exon 12 of 15	ENSP00000408399.2	P15170-2
	GSPT1	ENST00000420576.6	TSL:1	c.1181A>G	p.Asp394Gly	missense	Exon 12 of 15	ENSP00000399539.2	P15170-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		7.6
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.28		Loss of sheet (P = 0.0181)
MVP		0.82
MPC		2.9
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.87
gMVP		0.77

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

Other links and lift over

dbSNP: rs774096473; hg19: chr16-11971271;