rs1063739

chr8-144504344-C-Achr8-144504344-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005309.3(GPT):c.40C>A(p.His14Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,610,178 control chromosomes in the GnomAD database, including 178,460 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H14D) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.42 (14304 hom., cov: 35)
  • Exomes 𝑓: 0.47 (164156 hom.)
• Consequence: GPT NM_005309.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

Genes affected

GPT (HGNC:4552): (glutamic--pyruvic transaminase) This gene encodes cytosolic alanine aminotransaminase 1 (ALT1); also known as glutamate-pyruvate transaminase 1. This enzyme catalyzes the reversible transamination between alanine and 2-oxoglutarate to generate pyruvate and glutamate and, therefore, plays a key role in the intermediary metabolism of glucose and amino acids. Serum activity levels of this enzyme are routinely used as a biomarker of liver injury caused by drug toxicity, infection, alcohol, and steatosis. A related gene on chromosome 16 encodes a putative mitochondrial alanine aminotransaminase.[provided by RefSeq, Nov 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.262394E-5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPT	NM_005309.3	c.40C>A	p.His14Asn	missense_variant	1/11	ENST00000394955.3
LOC101928953	XR_007061149.1	n.103+1028G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPT	ENST00000394955.3	c.40C>A	p.His14Asn	missense_variant	1/11	1	NM_005309.3	P1
	ENST00000527086.1	n.187+621G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63355 AN: 152052 Hom.: 14299 Cov.: 35

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.446

GnomAD3 exomes AF: 0.482 AC: 119112 AN: 247036 Hom.: 29518 AF XY: 0.487 AC XY: 65323 AN XY: 134238

Gnomad AFR exome AF: 0.226

Gnomad AMR exome AF: 0.567

Gnomad ASJ exome AF: 0.456

Gnomad EAS exome AF: 0.494

Gnomad SAS exome AF: 0.557

Gnomad FIN exome AF: 0.493

Gnomad NFE exome AF: 0.472

Gnomad OTH exome AF: 0.470

GnomAD4 exome AF: 0.471 AC: 687172 AN: 1458008 Hom.: 164156 Cov.: 56 AF XY: 0.475 AC XY: 344635 AN XY: 725480

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.446

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.495

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.417 AC: 63383 AN: 152170 Hom.: 14304 Cov.: 35 AF XY: 0.423 AC XY: 31450 AN XY: 74402

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.443

Alfa AF: 0.466 Hom.: 31416

Bravo AF: 0.410

TwinsUK AF: 0.460 AC: 1704

ALSPAC AF: 0.471 AC: 1814

ESP6500AA AF: 0.232 AC: 1020

ESP6500EA AF: 0.465 AC: 4001

ExAC AF: 0.472 AC: 57114

Asia WGS AF: 0.538 AC: 1870 AN: 3478

EpiCase AF: 0.472

EpiControl AF: 0.474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	2.8
Dann	Benign	0.55
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
MetaRNN	Benign	0.000063	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.9	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	1.6	N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.15
MPC		0.068
ClinPred		0.0029	T
GERP RS		3.9
Varity_R		0.037
gMVP		0.51

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: rs1063739; hg19: chr8-145729727; COSMIC: COSV52952357; COSMIC: COSV52952357;