rs144202274

Variant names:

• chr13-48001480-A-AT
• rs144202274
• ENST00000423869.2:n.93dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000646804.1(SUCLA2):​c.-84-4458dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 601,148 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (16 hom., cov: 34)
  • Exomes 𝑓: 0.00079 (2 hom.)
• Consequence: SUCLA2 ENST00000646804.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.78
• Publications: 0 publications found

Genes affected

SUCLA2-AS1 (HGNC:39965): (SUCLA2 antisense RNA 1)

SUCLA2 (HGNC:11448): (succinate-CoA ligase ADP-forming subunit beta) Succinyl-CoA synthetase (SCS) is a mitochondrial matrix enzyme that acts as a heterodimer, being composed of an invariant alpha subunit and a substrate-specific beta subunit. The protein encoded by this gene is an ATP-specific SCS beta subunit that dimerizes with the SCS alpha subunit to form SCS-A, an essential component of the tricarboxylic acid cycle. SCS-A hydrolyzes ATP to convert succinate to succinyl-CoA. Defects in this gene are a cause of myopathic mitochondrial DNA depletion syndrome. A pseudogene of this gene has been found on chromosome 6. [provided by RefSeq, Jul 2008]

SUCLA2 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

  Inheritance: AR, Mitochondrial Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 13-48001480-A-AT is Benign according to our data. Variant chr13-48001480-A-AT is described in ClinVar as Likely_benign. ClinVar VariationId is 1208581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00631 (962/152354) while in subpopulation AFR AF = 0.0216 (899/41598). AF 95% confidence interval is 0.0204. There are 16 homozygotes in GnomAd4. There are 455 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 Mitochondrial,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000646804.1. 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
	SUCLA2-AS1	NR_189308.1		n.77dupT		non_coding_transcript_exon	Exon 1 of 2
	SUCLA2	NM_003850.3	MANE Select	c.-212dupA		upstream_gene	N/A	NP_003841.1	E5KS60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLA2-AS1	ENST00000423869.2	TSL:1	n.93dupT		non_coding_transcript_exon	Exon 1 of 2
	SUCLA2	ENST00000646804.1		c.-84-4458dupA		intron	N/A	ENSP00000493977.1	A0A2R8YDQ9
	SUCLA2	ENST00000643246.1		c.-84-4458dupA		intron	N/A	ENSP00000496235.1	A0A2R8YF84

Frequencies

GnomAD3 genomes AF: 0.00627 AC: 955 AN: 152236 Hom.: 15 Cov.: 34

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.000787 AC: 353 AN: 448794 Hom.: 2 Cov.: 4 AF XY: 0.000669 AC XY: 158 AN XY: 236174

African (AFR) AF: 0.0210 AC: 258 AN: 12270

American (AMR) AF: 0.00166 AC: 31 AN: 18680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13500

East Asian (EAS) AF: 0.00 AC: 0 AN: 30530

South Asian (SAS) AF: 0.0000653 AC: 3 AN: 45970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29156

Middle Eastern (MID) AF: 0.00155 AC: 3 AN: 1940

European-Non Finnish (NFE) AF: 0.0000775 AC: 21 AN: 271010

Other (OTH) AF: 0.00144 AC: 37 AN: 25738

GnomAD4 genome AF: 0.00631 AC: 962 AN: 152354 Hom.: 16 Cov.: 34 AF XY: 0.00611 AC XY: 455 AN XY: 74500

African (AFR) AF: 0.0216 AC: 899 AN: 41598

American (AMR) AF: 0.00287 AC: 44 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68034

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.000575 Hom.: 0

Bravo AF: 0.00722

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs144202274; hg19: chr13-48575616;