8-144504838-G-C

Variant names:

• chr8-144504838-G-C
• rs112574791
• NM_005309.3:c.320G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005309.3(GPT):​c.320G>C​(p.Arg107Thr) 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 1,461,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R107K) has been classified as Benign.

• 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: 2.14

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPT	NM_005309.3	c.320G>C	p.Arg107Thr	missense_variant	Exon 3 of 11	ENST00000394955.3	NP_005300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPT	ENST00000394955.3	c.320G>C	p.Arg107Thr	missense_variant	Exon 3 of 11	1	NM_005309.3	ENSP00000378408.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461204 Hom.: 0 Cov.: 39 AF XY: 0.00000138 AC XY: 1 AN XY: 726914

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 34

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.71	D;D
Eigen	Uncertain	0.40
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.97	.;D
M_CAP	Pathogenic	0.46	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Pathogenic	3.3	M;M
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.99	D;D
Vest4		0.63
MutPred		0.68		Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);
MVP		0.88
MPC		0.41
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.64
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs112574791; hg19: chr8-145730221;