16-58718562-C-T

Position:

• chr16-58718562-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000245206.10(GOT2):​c.562G>A​(p.Gly188Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0736 in 1,596,714 control chromosomes in the GnomAD database, including 4,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.057 (299 hom., cov: 33)
  • Exomes 𝑓: 0.075 (4460 hom.)
• Consequence: GOT2 ENST00000245206.10 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.04

Genes affected

GOT2 (HGNC:4433): (glutamic-oxaloacetic transaminase 2) Glutamic-oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and inner-membrane 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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035402477).
• BP6: Variant 16-58718562-C-T is Benign according to our data. Variant chr16-58718562-C-T is described in ClinVar as [Benign]. Clinvar id is 1555382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOT2	NM_002080.4	c.562G>A	p.Gly188Ser	missense_variant	5/10	ENST00000245206.10	NP_002071.2
GOT2	NM_001286220.2	c.433G>A	p.Gly145Ser	missense_variant	4/9		NP_001273149.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOT2	ENST00000245206.10	c.562G>A	p.Gly188Ser	missense_variant	5/10	1	NM_002080.4	ENSP00000245206	P1

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8704 AN: 152120 Hom.: 299 Cov.: 33

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0410

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.00713

Gnomad SAS AF: 0.0873

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0799

Gnomad OTH AF: 0.0689

GnomAD3 exomes AF: 0.0612 AC: 14703 AN: 240202 Hom.: 575 AF XY: 0.0647 AC XY: 8393 AN XY: 129720

Gnomad AFR exome AF: 0.0305

Gnomad AMR exome AF: 0.0261

Gnomad ASJ exome AF: 0.0350

Gnomad EAS exome AF: 0.00679

Gnomad SAS exome AF: 0.0917

Gnomad FIN exome AF: 0.0581

Gnomad NFE exome AF: 0.0799

Gnomad OTH exome AF: 0.0549

GnomAD4 exome AF: 0.0754 AC: 108880 AN: 1444476 Hom.: 4460 Cov.: 32 AF XY: 0.0757 AC XY: 54275 AN XY: 716772

Gnomad4 AFR exome AF: 0.0277

Gnomad4 AMR exome AF: 0.0276

Gnomad4 ASJ exome AF: 0.0353

Gnomad4 EAS exome AF: 0.00603

Gnomad4 SAS exome AF: 0.0898

Gnomad4 FIN exome AF: 0.0582

Gnomad4 NFE exome AF: 0.0825

Gnomad4 OTH exome AF: 0.0636

GnomAD4 genome AF: 0.0571 AC: 8695 AN: 152238 Hom.: 299 Cov.: 33 AF XY: 0.0563 AC XY: 4187 AN XY: 74432

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.00696

Gnomad4 SAS AF: 0.0861

Gnomad4 FIN AF: 0.0586

Gnomad4 NFE AF: 0.0799

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0690 Hom.: 226

Bravo AF: 0.0534

TwinsUK AF: 0.0850 AC: 315

ALSPAC AF: 0.0854 AC: 329

ESP6500AA AF: 0.0316 AC: 139

ESP6500EA AF: 0.0791 AC: 680

ExAC AF: 0.0633 AC: 7684

Asia WGS AF: 0.0520 AC: 180 AN: 3478

EpiCase AF: 0.0751

EpiControl AF: 0.0765

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

GOT2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 14, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T;T
MetaRNN	Benign	0.0035	T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.42
Sift	Benign	0.043	D;D
Sift4G	Benign	0.097	T;T
Polyphen		0.73	P;.
Vest4		0.052
MPC		0.67
ClinPred		0.025	T
GERP RS		5.7
Varity_R		0.77
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs11076256; hg19: chr16-58752466;