NM_001304431.2:c.250G>A

Variant names:

• chr5-58494786-G-A
• rs772963136
• NM_001304431.2:c.250G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001304431.2(GAPT):​c.250G>A​(p.Val84Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V84L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GAPT NM_001304431.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049161404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAPT	NM_001304431.2	c.250G>A	p.Val84Ile	missense_variant	Exon 3 of 3	ENST00000502276.6	NP_001291360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAPT	ENST00000502276.6	c.250G>A	p.Val84Ile	missense_variant	Exon 3 of 3	4	NM_001304431.2	ENSP00000423113.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250504 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135364

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.1
DANN	Benign	0.39
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.31	.;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.82	N;N
REVEL	Benign	0.039
Sift	Benign	0.11	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.0020	B;B
Vest4		0.048
MutPred		0.079		Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP		0.088
MPC		0.12
ClinPred		0.053	T
GERP RS		-1.6
Varity_R		0.032
gMVP		0.076

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

Other links and lift over

dbSNP: rs772963136; hg19: chr5-57790613;