chr13-47943154-A-G

Variant names:

• chr13-47943154-A-G
• rs4941618
• NM_003850.3:c.*217T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003850.3(SUCLA2):​c.*217T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 511,802 control chromosomes in the GnomAD database, including 222,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (66666 hom., cov: 32)
  • Exomes 𝑓: 0.93 (155930 hom.)
• Consequence: SUCLA2 NM_003850.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.30

Genes affected

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 13-47943154-A-G is Benign according to our data. Variant chr13-47943154-A-G is described in ClinVar as [Benign]. Clinvar id is 312262.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	NM_003850.3	c.*217T>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000646932.1	NP_003841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLA2	ENST00000646932	c.*217T>C		3_prime_UTR_variant	Exon 11 of 11		NM_003850.3	ENSP00000494360.1

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142344 AN: 152146 Hom.: 66615 Cov.: 32

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.946

GnomAD4 exome AF: 0.931 AC: 334609 AN: 359538 Hom.: 155930 Cov.: 4 AF XY: 0.927 AC XY: 176061 AN XY: 189874

Gnomad4 AFR exome AF: 0.951

Gnomad4 AMR exome AF: 0.936

Gnomad4 ASJ exome AF: 0.955

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.880

Gnomad4 FIN exome AF: 0.923

Gnomad4 NFE exome AF: 0.929

Gnomad4 OTH exome AF: 0.935

GnomAD4 genome AF: 0.936 AC: 142453 AN: 152264 Hom.: 66666 Cov.: 32 AF XY: 0.935 AC XY: 69618 AN XY: 74438

Gnomad4 AFR AF: 0.948

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.920

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.947

Alfa AF: 0.931 Hom.: 64027

Bravo AF: 0.939

Asia WGS AF: 0.944 AC: 3285 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.8
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4941618; hg19: chr13-48517289;