8-144504396-G-T

Variant names:

• chr8-144504396-G-T
• rs764916788
• NM_005309.3:c.92G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005309.3(GPT):​c.92G>T​(p.Arg31Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R31Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GPT NM_005309.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21367165).

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.92G>T	p.Arg31Leu	missense	Exon 1 of 11	NP_005300.1	P24298
	GPT	NM_001382664.1		c.92G>T	p.Arg31Leu	missense	Exon 2 of 12	NP_001369593.1	P24298
	GPT	NM_001382665.1		c.92G>T	p.Arg31Leu	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.92G>T	p.Arg31Leu	missense	Exon 1 of 11	ENSP00000378408.2	P24298
	GPT	ENST00000528431.5	TSL:1	c.92G>T	p.Arg31Leu	missense	Exon 2 of 12	ENSP00000433586.1	P24298
	GPT	ENST00000894981.1		c.92G>T	p.Arg31Leu	missense	Exon 1 of 11	ENSP00000565040.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459402 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 726102

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111914

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	11
DANN	Benign	0.74
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.57	N
PhyloP100		0.074
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.15
Sift	Benign	0.33	T
Sift4G	Benign	0.33	T
Polyphen		0.0050	B
Vest4		0.41
MutPred		0.43		Loss of MoRF binding (P = 0.0131)
MVP		0.68
MPC		0.11
ClinPred		0.37	T
GERP RS		2.2
PromoterAI		0.024	Neutral
Varity_R		0.094
gMVP		0.64
Mutation Taster		=90/10	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

dbSNP: rs764916788; hg19: chr8-145729779;