NM_003848.4:c.226+21789T>A

Variant names:

• chr3-67587666-A-T
• rs2363091
• NM_003848.4:c.226+21789T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003848.4(SUCLG2):​c.226+21789T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 152,248 control chromosomes in the GnomAD database, including 65,673 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 0.93 (65673 hom., cov: 32)
• Consequence: SUCLG2 NM_003848.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLG2	NM_003848.4	c.226+21789T>A		intron_variant	Intron 2 of 10	ENST00000307227.10	NP_003839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLG2	ENST00000307227.10	c.226+21789T>A		intron_variant	Intron 2 of 10	1	NM_003848.4	ENSP00000307432.5
SUCLG2	ENST00000493112.5	c.226+21789T>A		intron_variant	Intron 2 of 10	1		ENSP00000419325.1
SUCLG2	ENST00000492795.1	c.226+21789T>A		intron_variant	Intron 2 of 9	2		ENSP00000417589.1

Frequencies

GnomAD3 genomes AF: 0.927 AC: 140964 AN: 152130 Hom.: 65621 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.942

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

GnomAD4 genome AF: 0.927 AC: 141076 AN: 152248 Hom.: 65673 Cov.: 32 AF XY: 0.930 AC XY: 69203 AN XY: 74446

African (AFR) AF: 0.825 AC: 34241 AN: 41518

American (AMR) AF: 0.958 AC: 14642 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 3404 AN: 3472

East Asian (EAS) AF: 0.993 AC: 5155 AN: 5192

South Asian (SAS) AF: 0.960 AC: 4623 AN: 4816

European-Finnish (FIN) AF: 0.969 AC: 10279 AN: 10610

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.964 AC: 65598 AN: 68032

Other (OTH) AF: 0.941 AC: 1990 AN: 2114

Alfa AF: 0.941 Hom.: 8390

Bravo AF: 0.922

Asia WGS AF: 0.971 AC: 3373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.50
DANN	Benign	0.35
PhyloP100		-0.0080
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: rs2363091; hg19: chr3-67638090;