13-48001432-CG-C

Variant names:

• chr13-48001432-CG-C
• rs149342330
• ENST00000423869.1:n.47delG

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLA2-AS1	NR_189308.1	n.31delG		non_coding_transcript_exon_variant	Exon 1 of 2
SUCLA2	NM_003850.3	c.-164delC		upstream_gene_variant		ENST00000646932.1	NP_003841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLA2	ENST00000646932.1	c.-164delC		upstream_gene_variant			NM_003850.3	ENSP00000494360.1

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

Gnomad4 AFR exome AF: 0.0246

Gnomad4 AMR exome AF: 0.0685

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.00948

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.0741

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.114

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

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0764

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0238

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.0722

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0996 Hom.: 88

Bravo AF: 0.0811

Asia WGS AF: 0.138 AC: 478 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs149342330; hg19: chr13-48575568;