2-84449762-TAAAAAAAAAAAAAAA-TAAAAAAAAAA

Position:

• chr2-84449762-TAAAAAAAAAAAAAAA-TAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000393868.7(SUCLG1):​c.98-15_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 0.145 in 767,600 control chromosomes in the GnomAD database, including 422 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (322 hom., cov: 0)
  • Exomes 𝑓: 0.16 (100 hom.)
• Consequence: SUCLG1 ENST00000393868.7 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.74

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 -16 ACMG points.

• BP6: Variant 2-84449762-TAAAAA-T is Benign according to our data. Variant chr2-84449762-TAAAAA-T is described in ClinVar as [Benign]. Clinvar id is 403502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCLG1	NM_003849.4	c.98-15_98-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000393868.7	NP_003840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUCLG1	ENST00000393868.7	c.98-15_98-11del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003849.4	ENSP00000377446	P1

Frequencies

GnomAD3 genomes AF: 0.0666 AC: 6005 AN: 90100 Hom.: 319 Cov.: 0

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.0193

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.0627

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0858

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.0896

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0757

GnomAD4 exome AF: 0.155 AC: 105312 AN: 677494 Hom.: 100 AF XY: 0.155 AC XY: 54449 AN XY: 351572

Gnomad4 AFR exome AF: 0.192

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0667 AC: 6013 AN: 90106 Hom.: 322 Cov.: 0 AF XY: 0.0697 AC XY: 2898 AN XY: 41562

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0562

Gnomad4 ASJ AF: 0.0627

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.0855

Gnomad4 FIN AF: 0.0203

Gnomad4 NFE AF: 0.0182

Gnomad4 OTH AF: 0.0767

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;