chr13-48001557-G-T

Variant names:

• chr13-48001557-G-T
• rs7335797
• ENST00000423869.2:n.169G>T

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.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 ENST00000423869.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.847
• Publications: 6 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: Mitochondrial, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 684102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SUCLA2-AS1	NR_189308.1	n.153G>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLA2-AS1	ENST00000423869.2	n.169G>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
SUCLA2	ENST00000646804.1	c.-84-4534C>A		intron_variant	Intron 1 of 10			ENSP00000493977.1
SUCLA2	ENST00000643246.1	c.-84-4534C>A		intron_variant	Intron 2 of 2			ENSP00000496235.1

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

African (AFR) AF: 0.951 AC: 9428 AN: 9918

American (AMR) AF: 0.938 AC: 14613 AN: 15572

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 10486 AN: 10982

East Asian (EAS) AF: 0.999 AC: 23911 AN: 23932

South Asian (SAS) AF: 0.880 AC: 35356 AN: 40176

European-Finnish (FIN) AF: 0.925 AC: 21572 AN: 23332

Middle Eastern (MID) AF: 0.901 AC: 1405 AN: 1560

European-Non Finnish (NFE) AF: 0.930 AC: 200555 AN: 215720

Other (OTH) AF: 0.934 AC: 19841 AN: 21240

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

African (AFR) AF: 0.949 AC: 39460 AN: 41590

American (AMR) AF: 0.940 AC: 14389 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 3332 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5167 AN: 5184

South Asian (SAS) AF: 0.878 AC: 4243 AN: 4830

European-Finnish (FIN) AF: 0.920 AC: 9768 AN: 10618

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.927 AC: 63038 AN: 68034

Other (OTH) AF: 0.947 AC: 2003 AN: 2116

Alfa AF: 0.933 Hom.: 4874

Bravo AF: 0.939

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-0.85
PromoterAI		0.033	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: rs7335797; hg19: chr13-48575693;