13-48001557-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000423869.1(SUCLA2-AS1):n.169G>T 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 0.932 in 514,794 control chromosomes in the GnomAD database, including 223,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.94 (66703 hom., cov: 34)
  • Exomes 𝑓: 0.93 (157001 hom.)
• Consequence: SUCLA2-AS1 ENST00000423869.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.847

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-48001557-G-T is Benign according to our data. Variant chr13-48001557-G-T is described in ClinVar as [Benign]. Clinvar id is 684102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUCLA2-AS1	ENST00000423869.1	n.169G>T		non_coding_transcript_exon_variant	1/2	1
SUCLA2	ENST00000643246.1	c.-84-4534C>A		intron_variant
SUCLA2	ENST00000646804.1	c.-84-4534C>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142427 AN: 152244 Hom.: 66652 Cov.: 34

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.879

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.946

GnomAD4 exome AF: 0.930 AC: 337167 AN: 362432 Hom.: 157001 Cov.: 2 AF XY: 0.926 AC XY: 175448 AN XY: 189422

Gnomad4 AFR exome AF: 0.951

Gnomad4 AMR exome AF: 0.938

Gnomad4 ASJ exome AF: 0.955

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.880

Gnomad4 FIN exome AF: 0.925

Gnomad4 NFE exome AF: 0.930

Gnomad4 OTH exome AF: 0.934

GnomAD4 genome AF: 0.936 AC: 142536 AN: 152362 Hom.: 66703 Cov.: 34 AF XY: 0.935 AC XY: 69662 AN XY: 74494

Gnomad4 AFR AF: 0.949

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.920

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.947

Alfa AF: 0.912 Hom.: 964

Bravo AF: 0.939

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.87
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7335797; hg19: chr13-48575693;