2-84449762-TAA-T

Position:

• chr2-84449762-TAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003849.4(SUCLG1):​c.98-12_98-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 772,316 control chromosomes in the GnomAD database, including 322 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (300 hom., cov: 0)
  • Exomes 𝑓: 0.029 (22 hom.)
• Consequence: SUCLG1 NM_003849.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0610

Genes affected

SUCLG1 (HGNC:11449): (succinate-CoA ligase GDP/ADP-forming subunit alpha) This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile lactic acidosis and mitochondrial DNA depletion. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-84449762-TAA-T is Benign according to our data. Variant chr2-84449762-TAA-T is described in ClinVar as [Benign]. Clinvar id is 1296460.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUCLG1	NM_003849.4	c.98-12_98-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000393868.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUCLG1	ENST00000393868.7	c.98-12_98-11del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003849.4	P1

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 5379 AN: 89970 Hom.: 300 Cov.: 0

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.00249

Gnomad EAS AF: 0.0697

Gnomad SAS AF: 0.0107

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0142

Gnomad NFE AF: 0.00557

Gnomad OTH AF: 0.0500

GnomAD4 exome AF: 0.0289 AC: 19724 AN: 682338 Hom.: 22 AF XY: 0.0279 AC XY: 9910 AN XY: 354678

Gnomad4 AFR exome AF: 0.0844

Gnomad4 AMR exome AF: 0.0229

Gnomad4 ASJ exome AF: 0.0193

Gnomad4 EAS exome AF: 0.0270

Gnomad4 SAS exome AF: 0.0217

Gnomad4 FIN exome AF: 0.0167

Gnomad4 NFE exome AF: 0.0295

Gnomad4 OTH exome AF: 0.0290

GnomAD4 genome AF: 0.0598 AC: 5382 AN: 89978 Hom.: 300 Cov.: 0 AF XY: 0.0608 AC XY: 2522 AN XY: 41502

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.00249

Gnomad4 EAS AF: 0.0695

Gnomad4 SAS AF: 0.0107

Gnomad4 FIN AF: 0.0141

Gnomad4 NFE AF: 0.00557

Gnomad4 OTH AF: 0.0503

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs56733272; hg19: chr2-84676886;