chr16-58708287-G-A

Variant summary

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

The NM_002080.4(GOT2):​c.1177C>T​(p.Arg393Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,613,584 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R393Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

GOT2
NM_002080.4 missense

Scores

4
8
7

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.81
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=0.046020925).
BP6
Variant 16-58708287-G-A is Benign according to our data. Variant chr16-58708287-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1640898.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.1177C>T p.Arg393Trp missense_variant 10/10 ENST00000245206.10
GOT2NM_001286220.2 linkuse as main transcriptc.1048C>T p.Arg350Trp missense_variant 9/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GOT2ENST00000245206.10 linkuse as main transcriptc.1177C>T p.Arg393Trp missense_variant 10/101 NM_002080.4 P1P00505-1
GOT2ENST00000434819.2 linkuse as main transcriptc.1048C>T p.Arg350Trp missense_variant 9/92 P00505-2

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00198
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000292
AC:
73
AN:
250330
Hom.:
1
AF XY:
0.000229
AC XY:
31
AN XY:
135324
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00255
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.000656
GnomAD4 exome
AF:
0.000148
AC:
216
AN:
1461270
Hom.:
1
Cov.:
30
AF XY:
0.000128
AC XY:
93
AN XY:
726948
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00327
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.000381
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152314
Hom.:
0
Cov.:
33
AF XY:
0.000255
AC XY:
19
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00198
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000378
Hom.:
0
Bravo
AF:
0.0000529
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000305
AC:
37

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), LabcorpJun 08, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.47
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.59
D;.
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.24
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.86
D;D
M_CAP
Uncertain
0.21
D
MetaRNN
Benign
0.046
T;T
MetaSVM
Uncertain
0.53
D
MutationAssessor
Uncertain
2.7
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-5.8
D;D
REVEL
Pathogenic
0.65
Sift
Uncertain
0.0020
D;D
Sift4G
Benign
0.078
T;T
Polyphen
0.75
P;.
Vest4
0.60
MVP
0.95
MPC
0.45
ClinPred
0.26
T
GERP RS
2.6
Varity_R
0.77
gMVP
0.80

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: rs141302038; hg19: chr16-58742191; COSMIC: COSV99803895; COSMIC: COSV99803895; API