16-58708286-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002080.4(GOT2):​c.1178G>A​(p.Arg393Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,613,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R393W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

GOT2
NM_002080.4 missense

Scores

2
6
11

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.28
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 Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.020723939).
BP6
Variant 16-58708286-C-T is Benign according to our data. Variant chr16-58708286-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 747258.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GOT2NM_002080.4 linkuse as main transcriptc.1178G>A p.Arg393Gln missense_variant 10/10 ENST00000245206.10
GOT2NM_001286220.2 linkuse as main transcriptc.1049G>A p.Arg350Gln missense_variant 9/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GOT2ENST00000245206.10 linkuse as main transcriptc.1178G>A p.Arg393Gln missense_variant 10/101 NM_002080.4 P1P00505-1
GOT2ENST00000434819.2 linkuse as main transcriptc.1049G>A p.Arg350Gln missense_variant 9/92 P00505-2

Frequencies

GnomAD3 genomes
AF:
0.000808
AC:
123
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00268
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000207
AC:
52
AN:
250608
Hom.:
0
AF XY:
0.000125
AC XY:
17
AN XY:
135488
show subpopulations
Gnomad AFR exome
AF:
0.00234
Gnomad AMR exome
AF:
0.000319
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000122
AC:
179
AN:
1461496
Hom.:
0
Cov.:
30
AF XY:
0.000103
AC XY:
75
AN XY:
727064
show subpopulations
Gnomad4 AFR exome
AF:
0.00233
Gnomad4 AMR exome
AF:
0.000313
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000639
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.000814
AC:
124
AN:
152298
Hom.:
0
Cov.:
33
AF XY:
0.000819
AC XY:
61
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.00270
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000194
Hom.:
0
Bravo
AF:
0.000986
ESP6500AA
AF:
0.00182
AC:
8
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000247
AC:
30
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 03, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Uncertain
0.047
T
BayesDel_noAF
Pathogenic
0.29
CADD
Benign
23
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.39
T;.
Eigen
Benign
0.067
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.80
T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.021
T;T
MetaSVM
Uncertain
0.76
D
MutationAssessor
Benign
1.9
L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.9
N;N
REVEL
Uncertain
0.57
Sift
Benign
0.14
T;T
Sift4G
Benign
0.39
T;T
Polyphen
0.48
P;.
Vest4
0.14
MVP
0.93
MPC
0.46
ClinPred
0.024
T
GERP RS
5.7
Varity_R
0.65
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs151225545; hg19: chr16-58742190; API