NM_001304431.2:c.332T>C

Variant names:

• chr5-58494868-T-C
• NM_001304431.2:c.332T>C

Variant summary

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

The NM_001304431.2(GAPT):​c.332T>C​(p.Leu111Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: GAPT NM_001304431.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.332T>C	p.Leu111Pro	missense	Exon 3 of 3	NP_001291360.1	Q8N292
	GAPT	NM_001304428.2		c.332T>C	p.Leu111Pro	missense	Exon 3 of 3	NP_001291357.1	Q8N292
	GAPT	NM_001304429.2		c.332T>C	p.Leu111Pro	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.332T>C	p.Leu111Pro	missense	Exon 3 of 3	ENSP00000423113.2	Q8N292
	GAPT	ENST00000318469.2	TSL:6	c.332T>C	p.Leu111Pro	missense	Exon 1 of 1	ENSP00000323075.2	Q8N292
	GAPT	ENST00000396776.6	TSL:2	c.332T>C	p.Leu111Pro	missense	Exon 3 of 3	ENSP00000379997.2	Q8N292

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461672 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111904

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	0.33
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.022
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.9
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.37		Loss of helix (P = 0.0033)
MVP		0.51
MPC		0.61
ClinPred		0.90	D
GERP RS		5.2
Varity_R		0.90
gMVP		0.27
Mutation Taster		=84/16	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: chr5-57790695;