Genetic Variant GOT1:p.Gln370Glu (chr10-99397681-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002079.3(GOT1):c.1108C>G(p.Gln370Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,614,018 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 24 hom. )

Consequence

GOT1
NM_002079.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.90

Variant links:

Genes affected

GOT1 (HGNC:4432): (glutamic-oxaloacetic transaminase 1) Glutamic-oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and mitochondrial forms, GOT1 and GOT2, respectively. GOT plays a role in amino acid metabolism and the urea and tricarboxylic acid cycles. The two enzymes are homodimeric and show close homology. [provided by RefSeq, Jul 2008]

GOT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011169523).

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00125 (1821/1461710) while in subpopulation AMR AF= 0.0265 (1185/44722). AF 95% confidence interval is 0.0252. There are 24 homozygotes in gnomad4_exome. There are 777 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOT1	NM_002079.3 link	c.1108C>G	p.Gln370Glu	missense_variant	Exon 9 of 9	ENST00000370508.7	NP_002070.1	P17174-1A0A140VK69

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOT1	ENST00000370508.7 link	c.1108C>G	p.Gln370Glu	missense_variant	Exon 9 of 9	1	NM_002079.3	ENSP00000359539.5		P17174-1
GOT1	ENST00000489349.1 link	n.430C>G		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

214

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00518

AC:

1299

AN:

250626

Hom.:

AF XY:

0.00375

AC XY:

509

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.0299

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.0108

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00125

AC:

1821

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

777

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0265

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.0113

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000675

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.00141

AC:

214

AN:

152308

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0110

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000802

Hom.:

Bravo

AF:

0.00261

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00413

AC:

501

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.54

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.78

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.011

MetaSVM

Uncertain

0.73

MutationAssessor

Uncertain

2.8

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.5

REVEL

Pathogenic

0.89

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.031

Polyphen

0.99

Vest4

0.74

MVP

0.97

MPC

1.3

ClinPred

0.049

GERP RS

4.9

Varity_R

0.90

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over