3-67375866-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003848.4(SUCLG2):c.1184-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,611,836 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (10 hom., cov: 33)
  • Exomes 𝑓: 0.010 (139 hom.)
• Consequence: SUCLG2 NM_003848.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00007529
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.01

Genes affected

SUCLG2 (HGNC:11450): (succinate-CoA ligase GDP-forming subunit beta) This gene encodes a GTP-specific beta subunit of succinyl-CoA synthetase. Succinyl-CoA synthetase catalyzes the reversible reaction involving the formation of succinyl-CoA and succinate. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 5 and 12. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-67375866-G-A is Benign according to our data. Variant chr3-67375866-G-A is described in ClinVar as [Benign]. Clinvar id is 3056433.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00889 (1354/152308) while in subpopulation SAS AF= 0.0251 (121/4826). AF 95% confidence interval is 0.0214. There are 10 homozygotes in gnomad4. There are 668 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUCLG2	NM_003848.4	c.1184-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000307227.10
SUCLG2	XM_017007420.3	c.*596C>T		3_prime_UTR_variant	11/11
SUCLG2	NM_001177599.2	c.1184-15098C>T		intron_variant
SUCLG2	XM_047449140.1	c.1040-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUCLG2	ENST00000307227.10	c.1184-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003848.4	P1
SUCLG2	ENST00000460567.5	c.456-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
SUCLG2	ENST00000493112.5	c.1184-15098C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00888 AC: 1352 AN: 152190 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.0104 AC: 2550 AN: 245600 Hom.: 24 AF XY: 0.0116 AC XY: 1545 AN XY: 133060

Gnomad AFR exome AF: 0.00157

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.0109

Gnomad EAS exome AF: 0.000112

Gnomad SAS exome AF: 0.0220

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0113

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.0105 AC: 15304 AN: 1459528 Hom.: 139 Cov.: 36 AF XY: 0.0110 AC XY: 7951 AN XY: 725754

Gnomad4 AFR exome AF: 0.00170

Gnomad4 AMR exome AF: 0.00232

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0221

Gnomad4 FIN exome AF: 0.0219

Gnomad4 NFE exome AF: 0.00985

Gnomad4 OTH exome AF: 0.0119

GnomAD4 genome AF: 0.00889 AC: 1354 AN: 152308 Hom.: 10 Cov.: 33 AF XY: 0.00897 AC XY: 668 AN XY: 74478

Gnomad4 AFR AF: 0.00144

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0251

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.0110 Hom.: 8

Bravo AF: 0.00637

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SUCLG2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.1
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000075
dbscSNV1_RF	Benign	0.0
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: rs185820586; hg19: chr3-67426290;