13-47943043-T-C

Variant names:

• chr13-47943043-T-C
• rs13243
• NM_003850.3:c.*328A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003850.3(SUCLA2):​c.*328A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 302,492 control chromosomes in the GnomAD database, including 2,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (728 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1311 hom.)
• Consequence: SUCLA2 NM_003850.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.766
• Publications: 7 publications found

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]

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=-0.63).
• BP6: Variant 13-47943043-T-C is Benign according to our data. Variant chr13-47943043-T-C is described in ClinVar as Benign. ClinVar VariationId is 312259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003850.3. 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	NM_003850.3	MANE Select	c.*328A>G		3_prime_UTR	Exon 11 of 11	NP_003841.1	E5KS60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLA2	ENST00000646932.1	MANE Select	c.*328A>G		3_prime_UTR	Exon 11 of 11	ENSP00000494360.1	Q9P2R7-1
	SUCLA2	ENST00000643023.1		c.*328A>G		3_prime_UTR	Exon 12 of 12	ENSP00000495664.1	A0A2R8Y6Y7
	SUCLA2	ENST00000853364.1		c.*328A>G		3_prime_UTR	Exon 12 of 12	ENSP00000523423.1

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12879 AN: 152192 Hom.: 727 Cov.: 32

Gnomad AFR AF: 0.0262

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0769

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.119 AC: 17892 AN: 150182 Hom.: 1311 Cov.: 0 AF XY: 0.126 AC XY: 10052 AN XY: 79936

African (AFR) AF: 0.0265 AC: 122 AN: 4598

American (AMR) AF: 0.0780 AC: 429 AN: 5498

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 802 AN: 4168

East Asian (EAS) AF: 0.0147 AC: 112 AN: 7630

South Asian (SAS) AF: 0.185 AC: 4080 AN: 22014

European-Finnish (FIN) AF: 0.0784 AC: 573 AN: 7306

Middle Eastern (MID) AF: 0.146 AC: 83 AN: 568

European-Non Finnish (NFE) AF: 0.119 AC: 10721 AN: 90358

Other (OTH) AF: 0.121 AC: 970 AN: 8042

GnomAD4 genome AF: 0.0846 AC: 12888 AN: 152310 Hom.: 728 Cov.: 32 AF XY: 0.0847 AC XY: 6306 AN XY: 74494

African (AFR) AF: 0.0263 AC: 1095 AN: 41580

American (AMR) AF: 0.0767 AC: 1173 AN: 15296

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

East Asian (EAS) AF: 0.0237 AC: 123 AN: 5190

South Asian (SAS) AF: 0.180 AC: 867 AN: 4830

European-Finnish (FIN) AF: 0.0726 AC: 771 AN: 10618

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

European-Non Finnish (NFE) AF: 0.115 AC: 7814 AN: 68008

Other (OTH) AF: 0.109 AC: 231 AN: 2110

Alfa AF: 0.0416 Hom.: 34

Bravo AF: 0.0810

Asia WGS AF: 0.138 AC: 479 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13243; hg19: chr13-48517178;