2-84449762-TAAAAAAAAAAAAAAA-TAAAAAAAAAAA

Position:

• chr2-84449762-TAAAAAAAAAAAAAAA-TAAAAAAAAAAA

Variant summary

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

The NM_003849.4(SUCLG1):​c.98-14_98-11delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 783,810 control chromosomes in the GnomAD database, including 402 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (49 hom., cov: 0)
  • Exomes 𝑓: 0.23 (353 hom.)
• Consequence: SUCLG1 NM_003849.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.72

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]

SUCLG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-84449762-TAAAA-T is Benign according to our data. Variant chr2-84449762-TAAAA-T is described in ClinVar as [Benign]. Clinvar id is 440310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-84449762-TAAAA-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCLG1	NM_003849.4	c.98-14_98-11delTTTT		intron_variant		ENST00000393868.7	NP_003840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUCLG1	ENST00000393868.7	c.98-14_98-11delTTTT		intron_variant		1	NM_003849.4	ENSP00000377446.2

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 1993 AN: 90144 Hom.: 49 Cov.: 0

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00788

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.00420

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00331

Gnomad OTH AF: 0.0214

GnomAD4 exome AF: 0.230 AC: 159610 AN: 693660 Hom.: 353 AF XY: 0.227 AC XY: 81725 AN XY: 360742

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.0221 AC: 1991 AN: 90150 Hom.: 49 Cov.: 0 AF XY: 0.0228 AC XY: 948 AN XY: 41594

Gnomad4 AFR AF: 0.0589

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.00788

Gnomad4 EAS AF: 0.0498

Gnomad4 SAS AF: 0.0210

Gnomad4 FIN AF: 0.00420

Gnomad4 NFE AF: 0.00331

Gnomad4 OTH AF: 0.0212

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mitochondrial DNA depletion syndrome 9 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 08, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Aug 08, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 13, 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;