Genetic Variant GPT:p.His14Asp (chr8-144504344-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_005309.3(GPT):c.40C>G(p.His14Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GPT
NM_005309.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.72

Publications

44 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09554377).

BP6

Variant 8-144504344-C-G is Benign according to our data. Variant chr8-144504344-C-G is described in ClinVar as Benign. ClinVar VariationId is 16088.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPT	NM_005309.3 link	c.40C>G	p.His14Asp	missense_variant	Exon 1 of 11	ENST00000394955.3	NP_005300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPT	ENST00000394955.3 link	c.40C>G	p.His14Asp	missense_variant	Exon 1 of 11	1	NM_005309.3	ENSP00000378408.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

247036

AF XY:

0.00000745

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458174

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725556

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111802

Other (OTH)

AF:

0.00

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GPT POLYMORPHISM

Benign:1

Mar 01, 1997

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.18

.;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.096

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.34

N;N

PhyloP100

1.7

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.059

Sift

Benign

0.13

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.0

B;B

Vest4

0.12

MutPred

0.30

Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);

MVP

0.48

MPC

0.084

ClinPred

0.055

GERP RS

3.9

PromoterAI

-0.033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.053

gMVP

0.62

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over