NM_003848.4:c.758-10_758-8delCTT

Variant names:

• chr3-67498302-AAAG-A
• rs150352166
• NM_003848.4:c.758-10_758-8delCTT

Variant summary

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

The NM_003848.4(SUCLG2):​c.758-10_758-8delCTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 1,612,360 control chromosomes in the GnomAD database, including 9,121 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1686 hom., cov: 31)
  • Exomes 𝑓: 0.078 (7435 hom.)
• Consequence: SUCLG2 NM_003848.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.25
• Publications: 2 publications found

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

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

• BP6: Variant 3-67498302-AAAG-A is Benign according to our data. Variant chr3-67498302-AAAG-A is described in ClinVar as Benign. ClinVar VariationId is 257602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003848.4. 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
	SUCLG2	NM_003848.4	MANE Select	c.758-10_758-8delCTT		splice_region intron	N/A	NP_003839.2	Q96I99-1
	SUCLG2	NM_001177599.2		c.758-10_758-8delCTT		splice_region intron	N/A	NP_001171070.1	Q96I99-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG2	ENST00000307227.10	TSL:1 MANE Select	c.758-10_758-8delCTT		splice_region intron	N/A	ENSP00000307432.5	Q96I99-1
	SUCLG2	ENST00000493112.5	TSL:1	c.758-10_758-8delCTT		splice_region intron	N/A	ENSP00000419325.1	Q96I99-2
	SUCLG2	ENST00000460567.5	TSL:1	c.333+19942_333+19944delCTT		intron	N/A	ENSP00000417260.1	H0Y852

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18742 AN: 152032 Hom.: 1683 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0543

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0546

Gnomad OTH AF: 0.109

GnomAD2 exomes AF: 0.121 AC: 30052 AN: 247344 AF XY: 0.116

Gnomad AFR exome AF: 0.224

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.0708

Gnomad EAS exome AF: 0.307

Gnomad FIN exome AF: 0.0511

Gnomad NFE exome AF: 0.0535

Gnomad OTH exome AF: 0.0883

GnomAD4 exome AF: 0.0781 AC: 114021 AN: 1460210 Hom.: 7435 AF XY: 0.0794 AC XY: 57667 AN XY: 726382

African (AFR) AF: 0.226 AC: 7555 AN: 33386

American (AMR) AF: 0.218 AC: 9732 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.0748 AC: 1952 AN: 26092

East Asian (EAS) AF: 0.301 AC: 11936 AN: 39610

South Asian (SAS) AF: 0.167 AC: 14366 AN: 86090

European-Finnish (FIN) AF: 0.0528 AC: 2808 AN: 53216

Middle Eastern (MID) AF: 0.0585 AC: 337 AN: 5758

European-Non Finnish (NFE) AF: 0.0541 AC: 60061 AN: 1111180

Other (OTH) AF: 0.0874 AC: 5274 AN: 60314

GnomAD4 genome AF: 0.123 AC: 18771 AN: 152150 Hom.: 1686 Cov.: 31 AF XY: 0.127 AC XY: 9465 AN XY: 74398

African (AFR) AF: 0.221 AC: 9175 AN: 41472

American (AMR) AF: 0.152 AC: 2328 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3468

East Asian (EAS) AF: 0.310 AC: 1593 AN: 5146

South Asian (SAS) AF: 0.179 AC: 866 AN: 4830

European-Finnish (FIN) AF: 0.0543 AC: 576 AN: 10610

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0545 AC: 3709 AN: 68016

Other (OTH) AF: 0.109 AC: 231 AN: 2114

Alfa AF: 0.0835 Hom.: 142

Bravo AF: 0.138

Asia WGS AF: 0.245 AC: 853 AN: 3476

EpiCase AF: 0.0547

EpiControl AF: 0.0521

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		2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs150352166; hg19: chr3-67548726; COSMIC: COSV104407126;