rs6993

chr16-58707463-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002080.4(GOT2):c.*708T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,020 control chromosomes in the GnomAD database, including 26,791 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 0.59 (26790 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: GOT2 NM_002080.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOT2	NM_002080.4	c.*708T>C		3_prime_UTR_variant	10/10	ENST00000245206.10
GOT2	NM_001286220.2	c.*708T>C		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOT2	ENST00000245206.10	c.*708T>C		3_prime_UTR_variant	10/10	1	NM_002080.4	P1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89000 AN: 151896 Hom.: 26784 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.616

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.586 AC: 89024 AN: 152014 Hom.: 26790 Cov.: 32 AF XY: 0.579 AC XY: 43002 AN XY: 74304

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.611

Alfa AF: 0.630 Hom.: 32499

Bravo AF: 0.573

Asia WGS AF: 0.404 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	8.6
Dann	Benign	0.38

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: rs6993; hg19: chr16-58741367;