2-84449762-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAA

Variant names:

• chr2-84449762-TAA-T
• rs56733272
• NM_003849.4:c.98-12_98-11delTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003849.4(SUCLG1):​c.98-12_98-11delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 772,316 control chromosomes in the GnomAD database, including 322 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (300 hom., cov: 0)
  • Exomes 𝑓: 0.029 (22 hom.)
• Consequence: SUCLG1 NM_003849.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0610
• Publications: 3 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: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 2-84449762-TAA-T is Benign according to our data. Variant chr2-84449762-TAA-T is described in ClinVar as Benign. ClinVar VariationId is 1296460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG1	NM_003849.4	MANE Select	c.98-12_98-11delTT		intron	N/A	NP_003840.2	P53597

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG1	ENST00000393868.7	TSL:1 MANE Select	c.98-12_98-11delTT		intron	N/A	ENSP00000377446.2	P53597
	SUCLG1	ENST00000949558.1		c.98-12_98-11delTT		intron	N/A	ENSP00000619617.1
	SUCLG1	ENST00000912793.1		c.98-12_98-11delTT		intron	N/A	ENSP00000582852.1

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 5379 AN: 89970 Hom.: 300 Cov.: 0

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.00249

Gnomad EAS AF: 0.0697

Gnomad SAS AF: 0.0107

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0142

Gnomad NFE AF: 0.00557

Gnomad OTH AF: 0.0500

GnomAD4 exome AF: 0.0289 AC: 19724 AN: 682338 Hom.: 22 AF XY: 0.0279 AC XY: 9910 AN XY: 354678

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0844 AC: 1260 AN: 14934

American (AMR) AF: 0.0229 AC: 432 AN: 18854

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 307 AN: 15876

East Asian (EAS) AF: 0.0270 AC: 774 AN: 28628

South Asian (SAS) AF: 0.0217 AC: 973 AN: 44764

European-Finnish (FIN) AF: 0.0167 AC: 649 AN: 38872

Middle Eastern (MID) AF: 0.0332 AC: 74 AN: 2228

European-Non Finnish (NFE) AF: 0.0295 AC: 14350 AN: 487024

Other (OTH) AF: 0.0290 AC: 905 AN: 31158

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0598 AC: 5382 AN: 89978 Hom.: 300 Cov.: 0 AF XY: 0.0608 AC XY: 2522 AN XY: 41502

African (AFR) AF: 0.184 AC: 4600 AN: 24956

American (AMR) AF: 0.0239 AC: 200 AN: 8356

Ashkenazi Jewish (ASJ) AF: 0.00249 AC: 6 AN: 2410

East Asian (EAS) AF: 0.0695 AC: 206 AN: 2964

South Asian (SAS) AF: 0.0107 AC: 25 AN: 2330

European-Finnish (FIN) AF: 0.0141 AC: 37 AN: 2618

Middle Eastern (MID) AF: 0.0103 AC: 2 AN: 194

European-Non Finnish (NFE) AF: 0.00557 AC: 247 AN: 44356

Other (OTH) AF: 0.0503 AC: 59 AN: 1172

Alfa AF: 0.00569 Hom.: 848

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.061
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs56733272;

hg19: chr2-84676886;