5-58494931-A-G

Variant names:

• chr5-58494931-A-G
• NM_001304431.2:c.395A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304431.2(GAPT):​c.395A>G​(p.Asp132Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GAPT NM_001304431.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.839
• Publications: 0 publications found

Genes affected

GAPT (HGNC:26588): (GRB2 binding adaptor protein, transmembrane) Predicted to be involved in B cell homeostasis and B cell proliferation involved in immune response. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16812879).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304431.2. 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
	GAPT	NM_001304431.2	MANE Select	c.395A>G	p.Asp132Gly	missense	Exon 3 of 3	NP_001291360.1	Q8N292
	GAPT	NM_001304428.2		c.395A>G	p.Asp132Gly	missense	Exon 3 of 3	NP_001291357.1	Q8N292
	GAPT	NM_001304429.2		c.395A>G	p.Asp132Gly	missense	Exon 3 of 3	NP_001291358.1	Q8N292

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPT	ENST00000502276.6	TSL:4 MANE Select	c.395A>G	p.Asp132Gly	missense	Exon 3 of 3	ENSP00000423113.2	Q8N292
	GAPT	ENST00000318469.2	TSL:6	c.395A>G	p.Asp132Gly	missense	Exon 1 of 1	ENSP00000323075.2	Q8N292
	GAPT	ENST00000396776.6	TSL:2	c.395A>G	p.Asp132Gly	missense	Exon 3 of 3	ENSP00000379997.2	Q8N292

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.84
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.052
Sift	Benign	0.10	T
Sift4G	Benign	0.21	T
Polyphen		0.61	P
Vest4		0.15
MutPred		0.15		Gain of glycosylation at S131 (P = 0.0339)
MVP		0.18
MPC		0.24
ClinPred		0.67	D
GERP RS		1.1
Varity_R		0.14
gMVP		0.25
Mutation Taster		=100/0	polymorphism

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

hg19: chr5-57790758;