chr5-41731572-C-G

Variant names:

• chr5-41731572-C-G
• rs555729750
• NM_000436.4:c.*157G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000436.4(OXCT1):​c.*157G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000736 in 951,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: OXCT1 NM_000436.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.656
• 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 Gene-Disease associations (from GenCC):

• succinyl-CoA:3-ketoacid CoA transferase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Illumina, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.*157G>C		3_prime_UTR	Exon 17 of 17	NP_000427.1	P55809-1
	OXCT1	NM_001364299.2		c.*157G>C		3_prime_UTR	Exon 18 of 18	NP_001351228.1
	OXCT1	NM_001364300.2		c.*157G>C		3_prime_UTR	Exon 17 of 17	NP_001351229.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXCT1	ENST00000196371.10	TSL:1 MANE Select	c.*157G>C		3_prime_UTR	Exon 17 of 17	ENSP00000196371.5	P55809-1
	OXCT1	ENST00000972071.1		c.*157G>C		3_prime_UTR	Exon 18 of 18	ENSP00000642130.1
	OXCT1	ENST00000919063.1		c.*157G>C		3_prime_UTR	Exon 18 of 18	ENSP00000589122.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000736 AC: 7 AN: 951044 Hom.: 0 Cov.: 12 AF XY: 0.0000104 AC XY: 5 AN XY: 480356

African (AFR) AF: 0.00 AC: 0 AN: 21186

American (AMR) AF: 0.00 AC: 0 AN: 24074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19940

East Asian (EAS) AF: 0.00 AC: 0 AN: 32642

South Asian (SAS) AF: 0.0000329 AC: 2 AN: 60758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3064

European-Non Finnish (NFE) AF: 0.00000570 AC: 4 AN: 701434

Other (OTH) AF: 0.0000239 AC: 1 AN: 41906

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.61
PhyloP100		0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs555729750; hg19: chr5-41731674;