2-84439842-G-T

Variant names:

• chr2-84439842-G-T
• rs6721249
• NM_003849.4:c.589+1205C>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.589+1205C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 152,254 control chromosomes in the GnomAD database, including 472 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 0.053 (472 hom., cov: 32)
• Consequence: SUCLG1 NM_003849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLG1	NM_003849.4	c.589+1205C>A		intron_variant	Intron 5 of 8	ENST00000393868.7	NP_003840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLG1	ENST00000393868.7	c.589+1205C>A		intron_variant	Intron 5 of 8	1	NM_003849.4	ENSP00000377446.2
SUCLG1	ENST00000488234.1	n.46+1205C>A		intron_variant	Intron 1 of 1	3
SUCLG1	ENST00000651342.1	n.589+1205C>A		intron_variant	Intron 5 of 9			ENSP00000498471.1

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 8079 AN: 152136 Hom.: 465 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.0597

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0521

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

GnomAD4 genome AF: 0.0533 AC: 8122 AN: 152254 Hom.: 472 Cov.: 32 AF XY: 0.0531 AC XY: 3953 AN XY: 74448

African (AFR) AF: 0.142 AC: 5904 AN: 41516

American (AMR) AF: 0.0422 AC: 646 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0470 AC: 163 AN: 3468

East Asian (EAS) AF: 0.0116 AC: 60 AN: 5186

South Asian (SAS) AF: 0.0595 AC: 287 AN: 4824

European-Finnish (FIN) AF: 0.00396 AC: 42 AN: 10610

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0127 AC: 861 AN: 68032

Other (OTH) AF: 0.0539 AC: 114 AN: 2116

Alfa AF: 0.0163 Hom.: 12

Bravo AF: 0.0584

Asia WGS AF: 0.0510 AC: 176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.28
PhyloP100		0.044
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: rs6721249; hg19: chr2-84666966;