2-84449762-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAA

Position:

• chr2-84449762-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAA

Variant summary

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

The NM_003849.4(SUCLG1):​c.98-13_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 0.383 in 772,734 control chromosomes in the GnomAD database, including 28,306 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (25329 hom., cov: 0)
  • Exomes 𝑓: 0.34 (2977 hom.)
• Consequence: SUCLG1 NM_003849.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• 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 -16 ACMG points.

• BP6: Variant 2-84449762-TAAA-T is Benign according to our data. Variant chr2-84449762-TAAA-T is described in ClinVar as [Benign]. Clinvar id is 337162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-84449762-TAAA-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCLG1	NM_003849.4	c.98-13_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.98-13_98-11del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003849.4	ENSP00000377446	P1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 66527 AN: 90048 Hom.: 25340 Cov.: 0

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.746

GnomAD4 exome AF: 0.336 AC: 229157 AN: 682680 Hom.: 2977 AF XY: 0.330 AC XY: 116881 AN XY: 354582

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.739 AC: 66508 AN: 90054 Hom.: 25329 Cov.: 0 AF XY: 0.734 AC XY: 30496 AN XY: 41564

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.861

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.871

Gnomad4 NFE AF: 0.851

Gnomad4 OTH AF: 0.743

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mitochondrial DNA depletion syndrome 9 Benign:3

Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Apr 29, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 09, 2022	- -

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 12, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 29, 2018	- -

Mitochondrial DNA depletion syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;