8-144504344-C-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_005309.3(GPT):c.40C>G(p.His14Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H14N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GPT NM_005309.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• 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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09554377).
• BP6: Variant 8-144504344-C-G is Benign according to our data. Variant chr8-144504344-C-G is described in ClinVar as [Benign]. Clinvar id is 16088.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPT	NM_005309.3	c.40C>G	p.His14Asp	missense_variant	1/11	ENST00000394955.3
LOC101928953	XR_007061149.1	n.103+1028G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPT	ENST00000394955.3	c.40C>G	p.His14Asp	missense_variant	1/11	1	NM_005309.3	P1
	ENST00000527086.1	n.187+621G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD3 exomes AF: 0.00000405 AC: 1 AN: 247036 Hom.: 0 AF XY: 0.00000745 AC XY: 1 AN XY: 134238

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: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458174 Hom.: 0 Cov.: 56 AF XY: 0.00000276 AC XY: 2 AN XY: 725556

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GLUTAMIC PYRUVATE TRANSAMINASE POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Mar 01, 1997

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	15
Dann	Benign	0.82
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.076	N
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.34	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.059
Sift	Benign	0.13	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.30		Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);
MVP		0.48
MPC		0.084
ClinPred		0.055	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.053
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;