NM_005309.3:c.32C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 17/22 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

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 710733.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005309.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPT	NM_005309.3	MANE Select	c.32C>A	p.Ala11Glu	missense	Exon 1 of 11	NP_005300.1	P24298
GPT	NM_001382664.1		c.32C>A	p.Ala11Glu	missense	Exon 2 of 12	NP_001369593.1	P24298
GPT	NM_001382665.1		c.32C>A	p.Ala11Glu	missense	Exon 2 of 12	NP_001369594.1	P24298

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPT	ENST00000394955.3	TSL:1 MANE Select	c.32C>A	p.Ala11Glu	missense	Exon 1 of 11	ENSP00000378408.2	P24298
GPT	ENST00000528431.5	TSL:1	c.32C>A	p.Ala11Glu	missense	Exon 2 of 12	ENSP00000433586.1	P24298
GPT	ENST00000894981.1		c.32C>A	p.Ala11Glu	missense	Exon 1 of 11	ENSP00000565040.1

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

GnomAD2 exomes

AF:

0.00109

AC:

269

AN:

247264

AF XY:

0.00108

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 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

African (AFR)

AF:

0.000269

AC:

AN:

33472

American (AMR)

AF:

0.000872

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00237

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000300

AC:

AN:

49972

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00206

AC:

2289

AN:

1111864

Other (OTH)

AF:

0.000994

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

138

276

413

551

689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00132

AC:

201

AN:

152368

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41590

American (AMR)

AF:

0.00189

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00198

AC:

135

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00187

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

1.7

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.15

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.29

M_CAP

Benign

0.043

MetaRNN

Benign

0.0054

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

-0.12

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.59

REVEL

Benign

0.10

Sift

Benign

0.43

Sift4G

Benign

0.79

Polyphen

0.0

Vest4

0.17

MVP

0.44

MPC

0.072

ClinPred

0.0036

GERP RS

-0.048

PromoterAI

0.076

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.063

gMVP

0.47

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over