13-47954148-C-T

Position:

chr13-47954148-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003850.3(SUCLA2):c.1099G>A(p.Asp367Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,613,104 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 66 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 338 hom. )

Consequence

SUCLA2
NM_003850.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 7.51

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:

SUCLA2 (HGNC:):

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=0.004880607).

BP6

Variant 13-47954148-C-T is Benign according to our data. Variant chr13-47954148-C-T is described in ClinVar as [Benign]. Clinvar id is 139362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-47954148-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCLA2	NM_003850.3 linkuse as main transcript	c.1099G>A	p.Asp367Asn	missense_variant	8/11	ENST00000646932.1	NP_003841.1	Q9P2R7-1E5KS60Q9Y4T0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUCLA2	ENST00000646932.1 linkuse as main transcript	c.1099G>A	p.Asp367Asn	missense_variant	8/11		NM_003850.3	ENSP00000494360.1		Q9P2R7-1

Frequencies

GnomAD3 genomes

AF:

0.00936

AC:

1422

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00237

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0695

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.0427

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0170

AC:

4253

AN:

250876

Hom.:

184

AF XY:

0.0131

AC XY:

1778

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.0944

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.0460

Gnomad SAS exome

AF:

0.000883

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.00503

AC:

7353

AN:

1461038

Hom.:

338

Cov.:

AF XY:

0.00455

AC XY:

3305

AN XY:

726818

show subpopulations

Gnomad4 AFR exome

AF:

0.00150

Gnomad4 AMR exome

AF:

0.0957

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.0626

Gnomad4 SAS exome

AF:

0.000986

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000810

Gnomad4 OTH exome

AF:

0.00545

GnomAD4 genome

AF:

0.00942

AC:

1432

AN:

152066

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

791

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.0703

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.0424

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.0157

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0132

AC:

1607

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 30, 2011	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 28, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 29, 2017	- -

Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 11, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Jun 13, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;T;.;.;.;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

.;D;D;.;D;D

MetaRNN

Benign

0.0049

T;T;T;T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.4

M;M;.;.;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-4.4

.;D;.;.;.;D

REVEL

Pathogenic

0.73

Sift

Benign

0.10

.;T;.;.;.;T

Sift4G

Benign

0.086

.;T;.;.;.;T

Polyphen

0.88

P;P;.;.;.;.

Vest4

0.28

MPC

0.62

ClinPred

0.033

GERP RS

5.5

Varity_R

0.49

gMVP

0.91

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