5-41730285-C-A

Variant names:

• chr5-41730285-C-A
• rs10227
• NM_000436.4:c.*1444G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000436.4(OXCT1):​c.*1444G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00939 in 152,178 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0094 (23 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: OXCT1 NM_000436.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0720
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-41730285-C-A is Benign according to our data. Variant chr5-41730285-C-A is described in ClinVar as Benign. ClinVar VariationId is 353644.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00939 (1429/152178) while in subpopulation AFR AF = 0.0297 (1234/41534). AF 95% confidence interval is 0.0283. There are 23 homozygotes in GnomAd4. There are 671 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

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.*1444G>T		3_prime_UTR	Exon 17 of 17	NP_000427.1	P55809-1
	OXCT1	NM_001364299.2		c.*1444G>T		3_prime_UTR	Exon 18 of 18	NP_001351228.1
	OXCT1	NM_001364300.2		c.*1444G>T		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.*1444G>T		3_prime_UTR	Exon 17 of 17	ENSP00000196371.5	P55809-1
	OXCT1	ENST00000972071.1		c.*1444G>T		3_prime_UTR	Exon 18 of 18	ENSP00000642130.1
	OXCT1	ENST00000919063.1		c.*1444G>T		3_prime_UTR	Exon 18 of 18	ENSP00000589122.1

Frequencies

GnomAD3 genomes AF: 0.00936 AC: 1424 AN: 152060 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.00814

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00939 AC: 1429 AN: 152178 Hom.: 23 Cov.: 32 AF XY: 0.00902 AC XY: 671 AN XY: 74414

African (AFR) AF: 0.0297 AC: 1234 AN: 41534

American (AMR) AF: 0.00419 AC: 64 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10572

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00100 AC: 68 AN: 67992

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00379 Hom.: 1

Bravo AF: 0.0105

ClinVar

ClinVar submissions

Significance: 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	0.58
DANN	Benign	0.62
PhyloP100		-0.072
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10227; hg19: chr5-41730387;