16-58709462-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002080.4(GOT2):​c.1125C>T​(p.Thr375=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000851 in 1,613,782 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 5 hom., cov: 33)
Exomes 𝑓: 0.00049 ( 4 hom. )

Consequence

GOT2
NM_002080.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.767
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant 16-58709462-G-A is Benign according to our data. Variant chr16-58709462-G-A is described in ClinVar as [Benign]. Clinvar id is 1614801.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000489 (714/1461492) while in subpopulation AFR AF= 0.0172 (577/33478). AF 95% confidence interval is 0.0161. There are 4 homozygotes in gnomad4_exome. There are 321 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GOT2NM_002080.4 linkuse as main transcriptc.1125C>T p.Thr375= synonymous_variant 9/10 ENST00000245206.10
GOT2NM_001286220.2 linkuse as main transcriptc.996C>T p.Thr332= synonymous_variant 8/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GOT2ENST00000245206.10 linkuse as main transcriptc.1125C>T p.Thr375= synonymous_variant 9/101 NM_002080.4 P1P00505-1
GOT2ENST00000434819.2 linkuse as main transcriptc.996C>T p.Thr332= synonymous_variant 8/92 P00505-2
GOT2ENST00000494627.1 linkuse as main transcriptn.476C>T non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.00432
AC:
658
AN:
152172
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0147
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00573
GnomAD3 exomes
AF:
0.00115
AC:
288
AN:
251450
Hom.:
3
AF XY:
0.000927
AC XY:
126
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.0159
Gnomad AMR exome
AF:
0.000636
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000815
GnomAD4 exome
AF:
0.000489
AC:
714
AN:
1461492
Hom.:
4
Cov.:
31
AF XY:
0.000442
AC XY:
321
AN XY:
727016
show subpopulations
Gnomad4 AFR exome
AF:
0.0172
Gnomad4 AMR exome
AF:
0.000827
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00106
GnomAD4 genome
AF:
0.00433
AC:
659
AN:
152290
Hom.:
5
Cov.:
33
AF XY:
0.00411
AC XY:
306
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0147
Gnomad4 AMR
AF:
0.00196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00567
Alfa
AF:
0.00183
Hom.:
2
Bravo
AF:
0.00518
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 22, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
6.5
DANN
Benign
0.54
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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.

Other links and lift over

dbSNP: rs115659765; hg19: chr16-58743366; API