5-41870295-C-T

Variant names:

• chr5-41870295-C-T
• rs1750229851
• NM_000436.4:c.64G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000436.4(OXCT1):​c.64G>A​(p.Ala22Thr) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A22S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OXCT1 NM_000436.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 0 publications found

Genes affected

OXCT1 (HGNC:8527): (3-oxoacid CoA-transferase 1) This gene encodes a member of the 3-oxoacid CoA-transferase gene family. The encoded protein is a homodimeric mitochondrial matrix enzyme that plays a central role in extrahepatic ketone body catabolism by catalyzing the reversible transfer of coenzyme A from succinyl-CoA to acetoacetate. Mutations in this gene are associated with succinyl CoA:3-oxoacid CoA transferase deficiency. [provided by RefSeq, Jul 2008]

OXCT1-AS1 (HGNC:40423): (OXCT1 antisense RNA 1)

LOC102723752 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07829487).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000436.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXCT1	NM_000436.4	MANE Select	c.64G>A	p.Ala22Thr	missense	Exon 1 of 17	NP_000427.1	P55809-1
	OXCT1	NM_001364299.2		c.64G>A	p.Ala22Thr	missense	Exon 1 of 18	NP_001351228.1
	OXCT1	NM_001364301.2		c.64G>A	p.Ala22Thr	missense	Exon 1 of 17	NP_001351230.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXCT1	ENST00000196371.10	TSL:1 MANE Select	c.64G>A	p.Ala22Thr	missense	Exon 1 of 17	ENSP00000196371.5	P55809-1
	OXCT1	ENST00000972071.1		c.64G>A	p.Ala22Thr	missense	Exon 1 of 18	ENSP00000642130.1
	OXCT1	ENST00000919063.1		c.64G>A	p.Ala22Thr	missense	Exon 1 of 18	ENSP00000589122.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.4
DANN	Benign	0.67
DEOGEN2	Benign	0.075	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.39
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.091
Sift	Benign	0.61	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.31		Loss of helix (P = 0.0237)
MVP		0.40
MPC		0.66
ClinPred		0.070	T
GERP RS		0.91
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.064
gMVP		0.52
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1750229851; hg19: chr5-41870397;