chr1-39770247-G-T

Position:

• chr1-39770247-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022120.2(OXCT2):​c.1009C>A​(p.His337Asn) 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. 14/20 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: 17)
• Consequence: OXCT2 NM_022120.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3563586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXCT2	NM_022120.2	c.1009C>A	p.His337Asn	missense_variant	1/1	ENST00000327582.5	NP_071403.1
BMP8B	NM_001720.5	c.673+4061C>A		intron_variant		ENST00000372827.8	NP_001711.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXCT2	ENST00000327582.5	c.1009C>A	p.His337Asn	missense_variant	1/1	6	NM_022120.2	ENSP00000361914.1
BMP8B	ENST00000372827.8	c.673+4061C>A		intron_variant		1	NM_001720.5	ENSP00000361915.3

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 17

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 10, 2024

The c.1009C>A (p.H337N) alteration is located in exon 1 (coding exon 1) of the OXCT2 gene. This alteration results from a C to A substitution at nucleotide position 1009, causing the histidine (H) at amino acid position 337 to be replaced by an asparagine (N). 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	0.30
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Benign	0.51
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.17
Sift	Benign	0.30	T
Sift4G	Benign	0.31	T
Polyphen		0.023	B
Vest4		0.38
MutPred		0.31		Loss of loop (P = 0.1242);
MVP		0.89
ClinPred		0.61	D
GERP RS		-0.49
Varity_R		0.084
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-40235919;