8-144504336-C-T

Variant names:

• chr8-144504336-C-T
• rs139849083
• NM_005309.3:c.32C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005309.3(GPT):​c.32C>T​(p.Ala11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,610,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11E) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: GPT NM_005309.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 4 publications found

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]

ENSG00000255182 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04132846).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPT	NM_005309.3	MANE Select	c.32C>T	p.Ala11Val	missense	Exon 1 of 11	NP_005300.1	P24298
	GPT	NM_001382664.1		c.32C>T	p.Ala11Val	missense	Exon 2 of 12	NP_001369593.1	P24298
	GPT	NM_001382665.1		c.32C>T	p.Ala11Val	missense	Exon 2 of 12	NP_001369594.1	P24298

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPT	ENST00000394955.3	TSL:1 MANE Select	c.32C>T	p.Ala11Val	missense	Exon 1 of 11	ENSP00000378408.2	P24298
	GPT	ENST00000528431.5	TSL:1	c.32C>T	p.Ala11Val	missense	Exon 2 of 12	ENSP00000433586.1	P24298
	GPT	ENST00000894981.1		c.32C>T	p.Ala11Val	missense	Exon 1 of 11	ENSP00000565040.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152250 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000101 AC: 25 AN: 247264 AF XY: 0.0000893

Gnomad AFR exome AF: 0.000249

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.000105

Gnomad NFE exome AF: 0.0000978

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000187 AC: 273 AN: 1458160 Hom.: 0 Cov.: 30 AF XY: 0.000183 AC XY: 133 AN XY: 725562

African (AFR) AF: 0.000209 AC: 7 AN: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86254

European-Finnish (FIN) AF: 0.0000800 AC: 4 AN: 49972

Middle Eastern (MID) AF: 0.00245 AC: 14 AN: 5724

European-Non Finnish (NFE) AF: 0.000203 AC: 226 AN: 1111864

Other (OTH) AF: 0.000199 AC: 12 AN: 60346

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152368 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74504

African (AFR) AF: 0.000192 AC: 8 AN: 41590

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.000147

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.3
DANN	Benign	0.93
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.13	N
PhyloP100		-0.12
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.14
Sift	Benign	0.45	T
Sift4G	Benign	0.36	T
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.16		Loss of loop (P = 0.0203)
MVP		0.47
MPC		0.063
ClinPred		0.0055	T
GERP RS		-0.048
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.027
gMVP		0.40
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs139849083; hg19: chr8-145729719; COSMIC: COSV52954779; COSMIC: COSV52954779;