16-58709497-T-C

Variant summary

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

The NM_002080.4(GOT2):ā€‹c.1090A>Gā€‹(p.Lys364Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000259 in 1,613,934 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…).

Frequency

Genomes: š‘“ 0.00032 ( 0 hom., cov: 33)
Exomes š‘“: 0.00025 ( 1 hom. )

Consequence

GOT2
NM_002080.4 missense

Scores

1
8
10

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.92
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=0.010149479).
BP6
Variant 16-58709497-T-C is Benign according to our data. Variant chr16-58709497-T-C is described in ClinVar as [Benign]. Clinvar id is 2064625.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.1090A>G p.Lys364Glu missense_variant 9/10 ENST00000245206.10
GOT2NM_001286220.2 linkuse as main transcriptc.961A>G p.Lys321Glu missense_variant 8/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GOT2ENST00000245206.10 linkuse as main transcriptc.1090A>G p.Lys364Glu missense_variant 9/101 NM_002080.4 P1P00505-1
GOT2ENST00000434819.2 linkuse as main transcriptc.961A>G p.Lys321Glu missense_variant 8/92 P00505-2
GOT2ENST00000494627.1 linkuse as main transcriptn.441A>G non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.000315
AC:
48
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00732
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000767
AC:
193
AN:
251466
Hom.:
0
AF XY:
0.000647
AC XY:
88
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00973
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000253
AC:
370
AN:
1461618
Hom.:
1
Cov.:
30
AF XY:
0.000223
AC XY:
162
AN XY:
727108
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00804
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.000613
GnomAD4 genome
AF:
0.000315
AC:
48
AN:
152316
Hom.:
0
Cov.:
33
AF XY:
0.000389
AC XY:
29
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00734
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000445
Hom.:
0
Bravo
AF:
0.000521
ESP6500AA
AF:
0.00114
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000725
AC:
88
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 testingLabcorp Genetics (formerly Invitae), LabcorpJul 17, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Uncertain
0.020
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T;.
Eigen
Benign
-0.064
Eigen_PC
Benign
0.14
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.079
D
MetaRNN
Benign
0.010
T;T
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Benign
1.4
L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Uncertain
0.46
Sift
Benign
0.26
T;T
Sift4G
Benign
0.38
T;T
Polyphen
0.0020
B;.
Vest4
0.52
MVP
0.93
MPC
0.55
ClinPred
0.049
T
GERP RS
5.3
Varity_R
0.86
gMVP
0.75

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150122367; hg19: chr16-58743401; COSMIC: COSV99803546; COSMIC: COSV99803546; API