5-41853412-T-G

Variant names:

• chr5-41853412-T-G
• rs7723992
• NM_000436.4:c.414+7A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000436.4(OXCT1):​c.414+7A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 1,612,298 control chromosomes in the GnomAD database, including 6,945 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2560 hom., cov: 32)
  • Exomes 𝑓: 0.060 (4385 hom.)
• Consequence: OXCT1 NM_000436.4 splice_region, intron
• Scores: Splicing: ADA: 0.00006148
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.272
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-41853412-T-G is Benign according to our data. Variant chr5-41853412-T-G is described in ClinVar as Benign. ClinVar VariationId is 93004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

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.414+7A>C		splice_region intron	N/A	NP_000427.1	P55809-1
	OXCT1	NM_001364299.2		c.414+7A>C		splice_region intron	N/A	NP_001351228.1
	OXCT1	NM_001364300.2		c.435+7A>C		splice_region intron	N/A	NP_001351229.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXCT1	ENST00000196371.10	TSL:1 MANE Select	c.414+7A>C		splice_region intron	N/A	ENSP00000196371.5	P55809-1
	OXCT1	ENST00000972071.1		c.414+7A>C		splice_region intron	N/A	ENSP00000642130.1
	OXCT1	ENST00000919063.1		c.414+7A>C		splice_region intron	N/A	ENSP00000589122.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19937 AN: 152028 Hom.: 2557 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0555

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.122

GnomAD2 exomes AF: 0.0685 AC: 17200 AN: 251012 AF XY: 0.0650

Gnomad AFR exome AF: 0.343

Gnomad AMR exome AF: 0.0421

Gnomad ASJ exome AF: 0.0614

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0428

Gnomad NFE exome AF: 0.0550

Gnomad OTH exome AF: 0.0677

GnomAD4 exome AF: 0.0601 AC: 87720 AN: 1460152 Hom.: 4385 Cov.: 31 AF XY: 0.0596 AC XY: 43324 AN XY: 726482

African (AFR) AF: 0.349 AC: 11668 AN: 33388

American (AMR) AF: 0.0459 AC: 2051 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 1620 AN: 26112

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39676

South Asian (SAS) AF: 0.0645 AC: 5556 AN: 86196

European-Finnish (FIN) AF: 0.0400 AC: 2136 AN: 53334

Middle Eastern (MID) AF: 0.0757 AC: 436 AN: 5762

European-Non Finnish (NFE) AF: 0.0538 AC: 59726 AN: 1110660

Other (OTH) AF: 0.0749 AC: 4520 AN: 60322

GnomAD4 genome AF: 0.131 AC: 19961 AN: 152146 Hom.: 2560 Cov.: 32 AF XY: 0.127 AC XY: 9463 AN XY: 74422

African (AFR) AF: 0.336 AC: 13921 AN: 41460

American (AMR) AF: 0.0717 AC: 1096 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0547 AC: 264 AN: 4826

European-Finnish (FIN) AF: 0.0393 AC: 417 AN: 10612

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0548 AC: 3727 AN: 67992

Other (OTH) AF: 0.120 AC: 254 AN: 2114

Alfa AF: 0.0823 Hom.: 1592

Bravo AF: 0.145

Asia WGS AF: 0.0560 AC: 196 AN: 3478

EpiCase AF: 0.0604

EpiControl AF: 0.0583

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	Succinyl-CoA acetoacetate transferase deficiency (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.50
PhyloP100		0.27
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000061
dbscSNV1_RF	Benign	0.0
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: rs7723992; hg19: chr5-41853514;