dbSNP rs200124902: SUCLA2:p.Arg17Trp (chr13-48001221-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003850.3(SUCLA2):c.49C>T(p.Arg17Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,502 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R17G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SUCLA2
NM_003850.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.263

Publications

1 publications found

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-AS1 (HGNC:39965): (SUCLA2 antisense RNA 1)

SUCLA2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLA2	NM_003850.3 link	c.49C>T	p.Arg17Trp	missense_variant	Exon 1 of 11	ENST00000646932.1	NP_003841.1
SUCLA2-AS1	NR_189308.1 link	n.-184G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLA2	ENST00000646932.1 link	c.49C>T	p.Arg17Trp	missense_variant	Exon 1 of 11		NM_003850.3	ENSP00000494360.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000423

AC:

AN:

236526

AF XY:

0.00000774

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456502

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26000

East Asian (EAS)

AF:

0.00

AC:

AN:

39468

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85432

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110450

Other (OTH)

AF:

0.00

AC:

AN:

60080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000829

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

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

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.77

.;T;T;D;T;T;T

M_CAP

Pathogenic

0.98

MetaRNN

Uncertain

0.51

D;D;D;D;D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Benign

0.81

L;L;.;.;.;.;.

PhyloP100

0.26

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.90

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

REVEL

Uncertain

0.41

Sift

Uncertain

0.0090

.;D;.;D;.;.;.

Sift4G

Uncertain

0.0070

.;D;.;.;.;.;D

Polyphen

1.0

D;D;.;.;.;.;.

Vest4

0.57, 0.70

MutPred

0.54

Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);

MVP

0.73

MPC

0.82

ClinPred

0.85

GERP RS

2.4

PromoterAI

-0.080

Neutral

(source)

Varity_R

0.16

gMVP

0.60

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over