chr2-84449762-TAAAAAAA-T

Position:

• chr2-84449762-TAAAAAAA-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_003849.4(SUCLG1):​c.98-17_98-11delTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 781,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.016 (0 hom.)
• Consequence: SUCLG1 NM_003849.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter 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]

SUCLG1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-84449762-TAAAAAAA-T is Benign according to our data. Variant chr2-84449762-TAAAAAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 559371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0161 (11106/691790) while in subpopulation MID AF= 0.028 (63/2254). AF 95% confidence interval is 0.0249. There are 0 homozygotes in gnomad4_exome. There are 5663 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCLG1	NM_003849.4	c.98-17_98-11delTTTTTTT		intron_variant		ENST00000393868.7	NP_003840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUCLG1	ENST00000393868.7	c.98-17_98-11delTTTTTTT		intron_variant		1	NM_003849.4	ENSP00000377446.2

Frequencies

GnomAD3 genomes AF: 0.0000111 AC: 1 AN: 90114 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000426

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0161 AC: 11106 AN: 691790 Hom.: 0 AF XY: 0.0157 AC XY: 5663 AN XY: 359922

Gnomad4 AFR exome AF: 0.0270

Gnomad4 AMR exome AF: 0.0179

Gnomad4 ASJ exome AF: 0.0197

Gnomad4 EAS exome AF: 0.0219

Gnomad4 SAS exome AF: 0.0169

Gnomad4 FIN exome AF: 0.0129

Gnomad4 NFE exome AF: 0.0151

Gnomad4 OTH exome AF: 0.0199

GnomAD4 genome AF: 0.0000111 AC: 1 AN: 90114 Hom.: 0 Cov.: 0 AF XY: 0.0000241 AC XY: 1 AN XY: 41562

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000426

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Mar 16, 2016

- -

Mitochondrial DNA depletion syndrome 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 21, 2022

- -

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;