Variant 8-144504838-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.14

Variant links:

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]

GPT links:

ENSG00000255182 (HGNC:):

ENSG00000255182 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPT	NM_005309.3 link	c.320G>A	p.Arg107Lys	missense_variant	3/11	ENST00000394955.3	NP_005300.1	P24298

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPT	ENST00000394955.3 link	c.320G>A	p.Arg107Lys	missense_variant	3/11	1	NM_005309.3	ENSP00000378408.2		P24298

Frequencies

GnomAD3 genomes

AF:

0.00724

AC:

1102

AN:

152226

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00793

AC XY:

1077

AN XY:

135860

show subpopulations

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.:

AF XY:

0.0104

AC XY:

7528

AN XY:

726914

show subpopulations

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.:

Cov.:

AF XY:

0.00730

AC XY:

544

AN XY:

74496

show subpopulations

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.:

Bravo

AF:

0.00682

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00919

AC:

ExAC

AF:

0.00829

AC:

1007

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0129

EpiControl

AF:

0.0116

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.55

D;D

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.87

.;D

MetaRNN

Benign

0.011

T;T

MetaSVM

Uncertain

0.024

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Benign

0.46

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over