rs149342330

Variant names:

• chr13-48001432-CG-C
• rs149342330
• ENST00000423869.2:n.47delG

Your query was ambiguous. Multiple possible variants found:

• chr13-48001432-CG-C
• chr13-48001432-CG-CGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000646804.1(SUCLA2):​c.-84-4410delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 773,098 control chromosomes in the GnomAD database, including 5,028 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (725 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4303 hom.)
• Consequence: SUCLA2 ENST00000646804.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.55
• 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 13-48001432-CG-C is Benign according to our data. Variant chr13-48001432-CG-C is described in ClinVar as Benign. ClinVar VariationId is 1235212.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

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.31delG		non_coding_transcript_exon	Exon 1 of 2
	SUCLA2	NM_003850.3	MANE Select	c.-164delC		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.47delG		non_coding_transcript_exon	Exon 1 of 2
	SUCLA2	ENST00000646804.1		c.-84-4410delC		intron	N/A	ENSP00000493977.1	A0A2R8YDQ9
	SUCLA2	ENST00000643246.1		c.-84-4410delC		intron	N/A	ENSP00000496235.1	A0A2R8YF84

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12877 AN: 152162 Hom.: 724 Cov.: 32

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0722

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.108 AC: 66765 AN: 620818 Hom.: 4303 Cov.: 6 AF XY: 0.111 AC XY: 35798 AN XY: 321558

African (AFR) AF: 0.0246 AC: 396 AN: 16120

American (AMR) AF: 0.0685 AC: 1570 AN: 22926

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 2867 AN: 15766

East Asian (EAS) AF: 0.00948 AC: 301 AN: 31758

South Asian (SAS) AF: 0.177 AC: 9358 AN: 52796

European-Finnish (FIN) AF: 0.0741 AC: 2355 AN: 31790

Middle Eastern (MID) AF: 0.168 AC: 399 AN: 2382

European-Non Finnish (NFE) AF: 0.110 AC: 45913 AN: 415766

Other (OTH) AF: 0.114 AC: 3606 AN: 31514

GnomAD4 genome AF: 0.0846 AC: 12885 AN: 152280 Hom.: 725 Cov.: 32 AF XY: 0.0846 AC XY: 6300 AN XY: 74458

African (AFR) AF: 0.0263 AC: 1095 AN: 41594

American (AMR) AF: 0.0764 AC: 1169 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3472

East Asian (EAS) AF: 0.0238 AC: 123 AN: 5158

South Asian (SAS) AF: 0.181 AC: 871 AN: 4824

European-Finnish (FIN) AF: 0.0722 AC: 767 AN: 10616

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7814 AN: 67998

Other (OTH) AF: 0.110 AC: 232 AN: 2108

Alfa AF: 0.0935 Hom.: 102

Bravo AF: 0.0811

Asia WGS AF: 0.138 AC: 478 AN: 3478

ClinVar

ClinVar submissions

Significance: 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		-3.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs149342330;

hg19: chr13-48575568;