1-39770649-T-C

Position:

chr1-39770649-T-C

Variant summary

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

The NM_022120.2(OXCT2):c.607A>G(p.Ile203Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,520,494 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0016 ( 21 hom. )

Consequence

OXCT2
NM_022120.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

OXCT2 (HGNC:18606): (3-oxoacid CoA-transferase 2) The protein encoded by this gene catalyzes the transfer of a CoA group from succinate to acetoacetate and is an important enzyme in ketone body catabolism. The encoded protein localizes to the mitochondrion. This gene is intronless, and a pseudogene of this gene is located elsewhere on chromosome 1. [provided by RefSeq, Aug 2016]

OXCT2 links:

BMP8B (HGNC:1075): (bone morphogenetic protein 8b) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The encoded protein stimulates thermogenesis in brown adipose tissue. Expression of this gene may be downregulated in pancreatic cancer. This gene may have arose from a gene duplication event and its gene duplicate is also present on chromosome 1. [provided by RefSeq, Jul 2016]

BMP8B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02675119).

BP6

Variant 1-39770649-T-C is Benign according to our data. Variant chr1-39770649-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2638717.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXCT2	NM_022120.2 linkuse as main transcript	c.607A>G	p.Ile203Val	missense_variant	1/1	ENST00000327582.5	NP_071403.1	Q9BYC2
BMP8B	NM_001720.5 linkuse as main transcript	c.673+3659A>G		intron_variant		ENST00000372827.8	NP_001711.2	P34820-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXCT2	ENST00000327582.5 linkuse as main transcript	c.607A>G	p.Ile203Val	missense_variant	1/1	6	NM_022120.2	ENSP00000361914.1		Q9BYC2
BMP8B	ENST00000372827.8 linkuse as main transcript	c.673+3659A>G		intron_variant		1	NM_001720.5	ENSP00000361915.3		P34820-1

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

154

AN:

123190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00155

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000328

Gnomad FIN

AF:

0.00249

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00125

AC:

270

AN:

216020

Hom.:

AF XY:

0.00132

AC XY:

156

AN XY:

118492

show subpopulations

Gnomad AFR exome

AF:

0.000255

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000910

Gnomad FIN exome

AF:

0.00105

Gnomad NFE exome

AF:

0.00210

Gnomad OTH exome

AF:

0.000552

GnomAD4 exome

AF:

0.00158

AC:

2205

AN:

1397190

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1072

AN XY:

694430

show subpopulations

Gnomad4 AFR exome

AF:

0.000167

Gnomad4 AMR exome

AF:

0.000370

Gnomad4 ASJ exome

AF:

0.0000407

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000805

Gnomad4 FIN exome

AF:

0.00128

Gnomad4 NFE exome

AF:

0.00185

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.00125

AC:

154

AN:

123304

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

59294

show subpopulations

Gnomad4 AFR

AF:

0.000455

Gnomad4 AMR

AF:

0.00155

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000328

Gnomad4 FIN

AF:

0.00249

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00113

ESP6500AA

AF:

0.000466

AC:

ESP6500EA

AF:

0.00190

AC:

ExAC

AF:

0.00138

AC:

165

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2024

The c.607A>G (p.I203V) alteration is located in exon 1 (coding exon 1) of the OXCT2 gene. This alteration results from a A to G substitution at nucleotide position 607, causing the isoleucine (I) at amino acid position 203 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

BMP8B: BS2; OXCT2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.76

M_CAP

Benign

0.024

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.94

REVEL

Uncertain

0.29

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0070

Polyphen

0.69

Vest4

0.25

MVP

0.50

ClinPred

0.13

GERP RS

-0.15

Varity_R

0.28

gMVP

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over