rs555729750

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-41731572-C-T
• chr5-41731572-C-A
• chr5-41731572-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_000436.4(OXCT1):​c.*157G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,103,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: OXCT1 NM_000436.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-41731572-C-T is Benign according to our data. Variant chr5-41731572-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 353653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000789 (12/152148) while in subpopulation EAS AF = 0.00116 (6/5182). AF 95% confidence interval is 0.000503. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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>A		3_prime_UTR	Exon 17 of 17	NP_000427.1	P55809-1
	OXCT1	NM_001364299.2		c.*157G>A		3_prime_UTR	Exon 18 of 18	NP_001351228.1
	OXCT1	NM_001364300.2		c.*157G>A		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>A		3_prime_UTR	Exon 17 of 17	ENSP00000196371.5	P55809-1
	OXCT1	ENST00000972071.1		c.*157G>A		3_prime_UTR	Exon 18 of 18	ENSP00000642130.1
	OXCT1	ENST00000919063.1		c.*157G>A		3_prime_UTR	Exon 18 of 18	ENSP00000589122.1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 152032 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000326 AC: 31 AN: 951044 Hom.: 0 Cov.: 12 AF XY: 0.0000208 AC XY: 10 AN XY: 480356

African (AFR) AF: 0.000142 AC: 3 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: 0.000490 AC: 16 AN: 32642

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 701434

Other (OTH) AF: 0.000286 AC: 12 AN: 41906

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74376

African (AFR) AF: 0.000144 AC: 6 AN: 41524

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000756

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Succinyl-CoA acetoacetate transferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.33
PhyloP100		0.66
Mutation Taster		=100/0	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: rs555729750; hg19: chr5-41731674;