chr16-58708301-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

2
Splicing: ADA: 0.00003572
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.255
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]

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ACMG classification

Classification made for transcript

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 GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GOT2NM_002080.4 linkuse as main transcriptc.1171-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000245206.10
GOT2NM_001286220.2 linkuse as main transcriptc.1042-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GOT2ENST00000245206.10 linkuse as main transcriptc.1171-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_002080.4 P1P00505-1
GOT2ENST00000434819.2 linkuse as main transcriptc.1042-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 2 P00505-2

Frequencies

GnomAD3 genomes
AF:
0.00192
AC:
292
AN:
152244
Hom.:
4
Cov.:
33
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 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

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

Other links and lift over

dbSNP: rs188448255; hg19: chr16-58742205; API