rs2290174

Positions:

• chr3-67609616-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003848.4(SUCLG2):​c.85-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,605,558 control chromosomes in the GnomAD database, including 161,771 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (18780 hom., cov: 32)
  • Exomes 𝑓: 0.44 (142991 hom.)
• Consequence: SUCLG2 NM_003848.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.183

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-67609616-G-A is Benign according to our data. Variant chr3-67609616-G-A is described in ClinVar as [Benign]. Clinvar id is 257603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCLG2	NM_003848.4	c.85-20C>T		intron_variant		ENST00000307227.10	NP_003839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUCLG2	ENST00000307227.10	c.85-20C>T		intron_variant		1	NM_003848.4	ENSP00000307432	P1
SUCLG2	ENST00000493112.5	c.85-20C>T		intron_variant		1		ENSP00000419325
SUCLG2	ENST00000492795.1	c.85-20C>T		intron_variant		2		ENSP00000417589

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73611 AN: 151384 Hom.: 18739 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.453

GnomAD3 exomes AF: 0.414 AC: 101676 AN: 245440 Hom.: 22285 AF XY: 0.412 AC XY: 54885 AN XY: 133266

Gnomad AFR exome AF: 0.648

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.419

Gnomad SAS exome AF: 0.321

Gnomad FIN exome AF: 0.476

Gnomad NFE exome AF: 0.447

Gnomad OTH exome AF: 0.419

GnomAD4 exome AF: 0.438 AC: 636851 AN: 1454054 Hom.: 142991 Cov.: 32 AF XY: 0.435 AC XY: 314467 AN XY: 723506

Gnomad4 AFR exome AF: 0.652

Gnomad4 AMR exome AF: 0.246

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.403

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.479

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome AF: 0.486 AC: 73686 AN: 151504 Hom.: 18780 Cov.: 32 AF XY: 0.478 AC XY: 35381 AN XY: 74006

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.458

Alfa AF: 0.466 Hom.: 3178

Bravo AF: 0.485

Asia WGS AF: 0.413 AC: 1438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2290174; hg19: chr3-67660040; COSMIC: COSV56206085;