16-58708301-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002080.4(GOT2):c.1171-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,613,344 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (13 hom.)
• Consequence: GOT2 NM_002080.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003572
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.255

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-58708301-G-C is Benign according to our data. Variant chr16-58708301-G-C is described in ClinVar as [Benign]. Clinvar id is 734481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOT2	NM_002080.4	c.1171-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000245206.10
GOT2	NM_001286220.2	c.1042-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOT2	ENST00000245206.10	c.1171-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002080.4	P1
GOT2	ENST00000434819.2	c.1042-8C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00192 AC: 292 AN: 152244 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00177 AC: 441 AN: 249654 Hom.: 0 AF XY: 0.00179 AC XY: 241 AN XY: 134986

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000262

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0130

Gnomad NFE exome AF: 0.00125

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00168 AC: 2459 AN: 1460982 Hom.: 13 Cov.: 30 AF XY: 0.00168 AC XY: 1221 AN XY: 726804

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0128

Gnomad4 NFE exome AF: 0.00153

Gnomad4 OTH exome AF: 0.000961

GnomAD4 genome AF: 0.00192 AC: 292 AN: 152362 Hom.: 4 Cov.: 33 AF XY: 0.00251 AC XY: 187 AN XY: 74508

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.00154

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00134 Hom.: 0

Bravo AF: 0.000650

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 02, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.6
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000036
dbscSNV1_RF	Benign	0.0060
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: rs188448255; hg19: chr16-58742205;