rs61756204

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003850.3(SUCLA2):c.256A>G(p.Ile86Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000765 in 1,613,438 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 4 hom. )

Consequence

SUCLA2
NM_003850.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.85

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073103607).

BP6

Variant 13-47996858-T-C is Benign according to our data. Variant chr13-47996858-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 139364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00412 (628/152300) while in subpopulation AFR AF= 0.0145 (601/41574). AF 95% confidence interval is 0.0135. There are 1 homozygotes in gnomad4. There are 303 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 Mitochondrial gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLA2	NM_003850.3 link	c.256A>G	p.Ile86Val	missense_variant	Exon 2 of 11	ENST00000646932.1	NP_003841.1	Q9P2R7-1E5KS60Q9Y4T0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLA2	ENST00000646932.1 link	c.256A>G	p.Ile86Val	missense_variant	Exon 2 of 11		NM_003850.3	ENSP00000494360.1		Q9P2R7-1

Frequencies

GnomAD3 genomes

AF:

0.00413

AC:

628

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00117

AC:

294

AN:

251070

Hom.:

AF XY:

0.000766

AC XY:

104

AN XY:

135692

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000415

AC:

606

AN:

1461138

Hom.:

Cov.:

AF XY:

0.000352

AC XY:

256

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.000812

GnomAD4 genome

AF:

0.00412

AC:

628

AN:

152300

Hom.:

Cov.:

AF XY:

0.00407

AC XY:

303

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00467

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00148

AC:

180

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Mar 05, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 26, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 30, 2017

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

not specified

Benign:1

May 24, 2013

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

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.20

T;T;.;.;.;.;.;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.77

.;T;T;.;T;T;T;T

MetaRNN

Benign

0.0073

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.33

N;N;.;.;.;.;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.11

.;N;.;.;.;.;.;.

REVEL

Benign

0.079

Sift

Benign

0.69

.;T;.;.;.;.;.;.

Sift4G

Benign

0.59

.;T;.;.;.;.;.;T

Polyphen

0.0

B;B;.;.;.;.;.;.

Vest4

0.24, 0.23

MVP

0.36

MPC

0.24

ClinPred

0.0022

GERP RS

1.8

Varity_R

0.036

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over