1-39770390-T-C

Position:

• chr1-39770390-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022120.2(OXCT2):​c.866A>G​(p.Asp289Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 19)
• Consequence: OXCT2 NM_022120.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.269

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052415907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXCT2	NM_022120.2	c.866A>G	p.Asp289Gly	missense_variant	1/1	ENST00000327582.5	NP_071403.1
BMP8B	NM_001720.5	c.673+3918A>G		intron_variant		ENST00000372827.8	NP_001711.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXCT2	ENST00000327582.5	c.866A>G	p.Asp289Gly	missense_variant	1/1	6	NM_022120.2	ENSP00000361914.1
BMP8B	ENST00000372827.8	c.673+3918A>G		intron_variant		1	NM_001720.5	ENSP00000361915.3

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 19

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

The c.866A>G (p.D289G) 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 866, causing the aspartic acid (D) at amino acid position 289 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.3
DANN	Benign	0.35
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.13
Sift	Benign	0.31	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.046
MutPred		0.22		Loss of loop (P = 0.1258);
MVP		0.44
ClinPred		0.087	T
GERP RS		-4.9
Varity_R		0.061
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-40236062;