8-144504838-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005309.3(GPT):c.320G>A(p.Arg107Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,613,546 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (8 hom., cov: 34)
  • Exomes 𝑓: 0.011 (111 hom.)
• Consequence: GPT NM_005309.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011241674).
• BP6: Variant 8-144504838-G-A is Benign according to our data. Variant chr8-144504838-G-A is described in ClinVar as [Benign]. Clinvar id is 773406.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPT	NM_005309.3	c.320G>A	p.Arg107Lys	missense_variant	3/11	ENST00000394955.3
LOC101928953	XR_007061149.1	n.103+534C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPT	ENST00000394955.3	c.320G>A	p.Arg107Lys	missense_variant	3/11	1	NM_005309.3	P1
	ENST00000527086.1	n.187+127C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00724 AC: 1102 AN: 152226 Hom.: 8 Cov.: 34

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00706

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00857

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.00716

GnomAD3 exomes AF: 0.00781 AC: 1961 AN: 251240 Hom.: 14 AF XY: 0.00793 AC XY: 1077 AN XY: 135860

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00584

Gnomad ASJ exome AF: 0.00447

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000621

Gnomad FIN exome AF: 0.00768

Gnomad NFE exome AF: 0.0126

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0107 AC: 15617 AN: 1461202 Hom.: 111 Cov.: 39 AF XY: 0.0104 AC XY: 7528 AN XY: 726914

Gnomad4 AFR exome AF: 0.00173

Gnomad4 AMR exome AF: 0.00546

Gnomad4 ASJ exome AF: 0.00432

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000707

Gnomad4 FIN exome AF: 0.0103

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.00838

GnomAD4 genome AF: 0.00723 AC: 1102 AN: 152344 Hom.: 8 Cov.: 34 AF XY: 0.00730 AC XY: 544 AN XY: 74496

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.00705

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00857

Gnomad4 NFE AF: 0.0115

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.0111 Hom.: 13

Bravo AF: 0.00682

TwinsUK AF: 0.0113 AC: 42

ALSPAC AF: 0.0114 AC: 44

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.00919 AC: 79

ExAC AF: 0.00829 AC: 1007

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0129

EpiControl AF: 0.0116

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	19
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.55	D;D
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.56	D
MetaRNN	Benign	0.011	T;T
MetaSVM	Uncertain	0.024	D
MutationAssessor	Uncertain	2.0	M;M
MutationTaster	Benign	0.99	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.4	N;N
REVEL	Uncertain	0.42
Sift	Benign	0.054	T;T
Sift4G	Benign	0.083	T;T
Polyphen		0.019	B;B
Vest4		0.34
MVP		0.84
MPC		0.071
ClinPred		0.012	T
GERP RS		3.4
Varity_R		0.19
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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;