Genetic Variant GPT:p.Ala11Glu (chr8-144504336-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005309.3(GPT):c.32C>A(p.Ala11Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,610,528 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 3 hom. )

Consequence

GPT
NM_005309.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.124

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054024756).

BP6

Variant 8-144504336-C-A is Benign according to our data. Variant chr8-144504336-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 710733.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPT	NM_005309.3 link	c.32C>A	p.Ala11Glu	missense_variant	Exon 1 of 11	ENST00000394955.3	NP_005300.1	P24298

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPT	ENST00000394955.3 link	c.32C>A	p.Ala11Glu	missense_variant	Exon 1 of 11	1	NM_005309.3	ENSP00000378408.2		P24298

Frequencies

GnomAD3 genomes

AF:

0.00132

AC:

201

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00198

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00109

AC:

269

AN:

247264

Hom.:

AF XY:

0.00108

AC XY:

145

AN XY:

134414

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00250

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000314

Gnomad NFE exome

AF:

0.00180

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00170

AC:

2474

AN:

1458160

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1150

AN XY:

725564

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00206

Gnomad4 OTH exome

AF:

0.000994

GnomAD4 genome

AF:

0.00132

AC:

201

AN:

152368

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00198

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00186

Hom.:

Bravo

AF:

0.00142

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00106

AC:

128

EpiCase

AF:

0.00120

EpiControl

AF:

0.00219

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

1.7

DANN

Benign

0.71

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.29

.;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.10

Sift

Benign

0.43

T;T

Sift4G

Benign

0.79

T;T

Polyphen

0.0

B;B

Vest4

0.17

MVP

0.44

MPC

0.072

ClinPred

0.0036

GERP RS

-0.048

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.063

gMVP

0.47

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

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