NM_005309.3:c.40C>A

Variant names:

• chr8-144504344-C-A
• rs1063739
• NM_005309.3:c.40C>A

Variant summary

Our verdict is Benign. The variant received -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. 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. H14Y) has been classified as Uncertain significance.

• 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
• Publications: 44 publications found

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]

ENSG00000255182 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005309.3. 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
	GPT	NM_005309.3	MANE Select	c.40C>A	p.His14Asn	missense	Exon 1 of 11	NP_005300.1	P24298
	GPT	NM_001382664.1		c.40C>A	p.His14Asn	missense	Exon 2 of 12	NP_001369593.1	P24298
	GPT	NM_001382665.1		c.40C>A	p.His14Asn	missense	Exon 2 of 12	NP_001369594.1	P24298

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPT	ENST00000394955.3	TSL:1 MANE Select	c.40C>A	p.His14Asn	missense	Exon 1 of 11	ENSP00000378408.2	P24298
	GPT	ENST00000528431.5	TSL:1	c.40C>A	p.His14Asn	missense	Exon 2 of 12	ENSP00000433586.1	P24298
	GPT	ENST00000894981.1		c.40C>A	p.His14Asn	missense	Exon 1 of 11	ENSP00000565040.1

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

GnomAD2 exomes AF: 0.482 AC: 119112 AN: 247036 AF XY: 0.487

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 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

African (AFR) AF: 0.224 AC: 7494 AN: 33472

American (AMR) AF: 0.556 AC: 24862 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 11657 AN: 26120

East Asian (EAS) AF: 0.444 AC: 17616 AN: 39696

South Asian (SAS) AF: 0.556 AC: 47957 AN: 86246

European-Finnish (FIN) AF: 0.495 AC: 24740 AN: 50016

Middle Eastern (MID) AF: 0.362 AC: 2072 AN: 5718

European-Non Finnish (NFE) AF: 0.470 AC: 523052 AN: 1111714

Other (OTH) AF: 0.459 AC: 27722 AN: 60348

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

African (AFR) AF: 0.236 AC: 9826 AN: 41548

American (AMR) AF: 0.521 AC: 7961 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1488 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2537 AN: 5174

South Asian (SAS) AF: 0.576 AC: 2780 AN: 4826

European-Finnish (FIN) AF: 0.500 AC: 5292 AN: 10590

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32193 AN: 67948

Other (OTH) AF: 0.443 AC: 938 AN: 2116

Alfa AF: 0.457 Hom.: 62583

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 v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.000063	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.9	N
PhyloP100		1.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.15
MPC		0.068
ClinPred		0.0029	T
GERP RS		3.9
PromoterAI		0.0094	Neutral
Varity_R		0.037
gMVP		0.51
Mutation Taster		=100/0	polymorphism (auto)

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