ENST00000643584.1:n.*215-66163G>A – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000643584.1(SUCLA2):n.*215-66163G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,878 control chromosomes in the GnomAD database, including 13,458 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 13458 hom., cov: 32)

Consequence

SUCLA2
ENST00000643584.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.280

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLA2	ENST00000643584.1 link	n.*215-66163G>A		intron_variant	Intron 13 of 13			ENSP00000494987.1		Q9P2R7-1
SUCLA2	ENST00000647008.1 link	n.1238-6088G>A		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63405

AN:

151758

Hom.:

13444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.468

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.408

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.418

AC:

63464

AN:

151878

Hom.:

13458

Cov.:

AF XY:

0.418

AC XY:

31021

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.386

Gnomad4 AMR

AF:

0.413

Gnomad4 ASJ

AF:

0.315

Gnomad4 EAS

AF:

0.534

Gnomad4 SAS

AF:

0.370

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.433

Gnomad4 OTH

AF:

0.407

Alfa

AF:

0.428

Hom.:

9883

Bravo

AF:

0.419

Asia WGS

AF:

0.416

AC:

1446

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.8

DANN

Benign

0.59

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over