2-84446128-C-T

Variant names:

• chr2-84446128-C-T
• rs10210248
• NM_003849.4:c.202-2728G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003849.4(SUCLG1):​c.202-2728G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,176 control chromosomes in the GnomAD database, including 38,001 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.68 (38001 hom., cov: 33)
• Consequence: SUCLG1 NM_003849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial DNA depletion syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG1	NM_003849.4	MANE Select	c.202-2728G>A		intron	N/A	NP_003840.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG1	ENST00000393868.7	TSL:1 MANE Select	c.202-2728G>A		intron	N/A	ENSP00000377446.2
	SUCLG1	ENST00000949558.1		c.229-2728G>A		intron	N/A	ENSP00000619617.1
	SUCLG1	ENST00000912793.1		c.202-2728G>A		intron	N/A	ENSP00000582852.1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103904 AN: 152056 Hom.: 37991 Cov.: 33

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.709

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.683 AC: 103942 AN: 152176 Hom.: 38001 Cov.: 33 AF XY: 0.690 AC XY: 51326 AN XY: 74428

African (AFR) AF: 0.393 AC: 16318 AN: 41508

American (AMR) AF: 0.768 AC: 11735 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2726 AN: 3468

East Asian (EAS) AF: 0.898 AC: 4645 AN: 5172

South Asian (SAS) AF: 0.808 AC: 3898 AN: 4826

European-Finnish (FIN) AF: 0.812 AC: 8610 AN: 10608

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53759 AN: 67994

Other (OTH) AF: 0.707 AC: 1494 AN: 2112

Alfa AF: 0.758 Hom.: 74306

Bravo AF: 0.668

Asia WGS AF: 0.814 AC: 2832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.51
PhyloP100		-0.095
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10210248; hg19: chr2-84673252;