ENST00000423869.2:n.63G>C

Variant names:

• chr13-48001451-G-C
• rs2296573
• ENST00000423869.2:n.63G>C

Variant summary

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

The ENST00000423869.2(SUCLA2-AS1):​n.63G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 678,290 control chromosomes in the GnomAD database, including 13,387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4788 hom., cov: 34)
  • Exomes 𝑓: 0.17 (8599 hom.)
• Consequence: SUCLA2-AS1 ENST00000423869.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.186
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 13-48001451-G-C is Benign according to our data. Variant chr13-48001451-G-C is described in ClinVar as Benign. ClinVar VariationId is 676448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000423869.2. 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.47G>C		non_coding_transcript_exon	Exon 1 of 2
	SUCLA2	NM_003850.3	MANE Select	c.-182C>G		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.63G>C		non_coding_transcript_exon	Exon 1 of 2
	SUCLA2	ENST00000646804.1		c.-84-4428C>G		intron	N/A	ENSP00000493977.1	A0A2R8YDQ9
	SUCLA2	ENST00000643246.1		c.-84-4428C>G		intron	N/A	ENSP00000496235.1	A0A2R8YF84

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34933 AN: 152060 Hom.: 4787 Cov.: 34

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.173 AC: 91036 AN: 526112 Hom.: 8599 Cov.: 6 AF XY: 0.170 AC XY: 46863 AN XY: 275366

African (AFR) AF: 0.394 AC: 5582 AN: 14150

American (AMR) AF: 0.108 AC: 2316 AN: 21426

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 2502 AN: 14662

East Asian (EAS) AF: 0.176 AC: 5510 AN: 31276

South Asian (SAS) AF: 0.120 AC: 5923 AN: 49192

European-Finnish (FIN) AF: 0.132 AC: 3987 AN: 30210

Middle Eastern (MID) AF: 0.163 AC: 351 AN: 2150

European-Non Finnish (NFE) AF: 0.178 AC: 59594 AN: 334650

Other (OTH) AF: 0.186 AC: 5271 AN: 28396

GnomAD4 genome AF: 0.230 AC: 34953 AN: 152178 Hom.: 4788 Cov.: 34 AF XY: 0.223 AC XY: 16598 AN XY: 74416

African (AFR) AF: 0.389 AC: 16134 AN: 41496

American (AMR) AF: 0.138 AC: 2106 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 579 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1170 AN: 5162

South Asian (SAS) AF: 0.124 AC: 597 AN: 4830

European-Finnish (FIN) AF: 0.128 AC: 1362 AN: 10614

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12214 AN: 67994

Other (OTH) AF: 0.215 AC: 454 AN: 2112

Alfa AF: 0.0988 Hom.: 140

Bravo AF: 0.239

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.9
DANN	Benign	0.52
PhyloP100		0.19
PromoterAI		-0.28	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2296573; hg19: chr13-48575587; COSMIC: COSV66222948; COSMIC: COSV66222948;