rs6993

Variant names:

• chr16-58707463-A-G
• rs6993
• NM_002080.4:c.*708T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

GOT2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 82

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002080.4. 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
	GOT2	NM_002080.4	MANE Select	c.*708T>C		3_prime_UTR	Exon 10 of 10	NP_002071.2	P00505-1
	GOT2	NM_001286220.2		c.*708T>C		3_prime_UTR	Exon 9 of 9	NP_001273149.1	P00505-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOT2	ENST00000245206.10	TSL:1 MANE Select	c.*708T>C		3_prime_UTR	Exon 10 of 10	ENSP00000245206.5	P00505-1
	GOT2	ENST00000954610.1		c.*708T>C		3_prime_UTR	Exon 11 of 11	ENSP00000624669.1
	GOT2	ENST00000857880.1		c.*708T>C		3_prime_UTR	Exon 10 of 10	ENSP00000527939.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 3 AN: 6

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.554 AC: 22980 AN: 41466

American (AMR) AF: 0.486 AC: 7420 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2554 AN: 3468

East Asian (EAS) AF: 0.234 AC: 1209 AN: 5174

South Asian (SAS) AF: 0.607 AC: 2928 AN: 4824

European-Finnish (FIN) AF: 0.579 AC: 6106 AN: 10542

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43736 AN: 67972

Other (OTH) AF: 0.611 AC: 1288 AN: 2108

Alfa AF: 0.621 Hom.: 45781

Bravo AF: 0.573

Asia WGS AF: 0.404 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.6
DANN	Benign	0.38
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6993; hg19: chr16-58741367;