chr3-67375866-G-T

Variant names:

• chr3-67375866-G-T
• rs185820586
• NM_003848.4:c.1184-7C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003848.4(SUCLG2):​c.1184-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SUCLG2 NM_003848.4 splice_region, intron
• Scores: Splicing: ADA: 0.00007529
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLG2	NM_003848.4	c.1184-7C>A		splice_region_variant, intron_variant	Intron 10 of 10	ENST00000307227.10	NP_003839.2
SUCLG2	XM_017007420.3	c.*596C>A		3_prime_UTR_variant	Exon 11 of 11		XP_016862909.1
SUCLG2	NM_001177599.2	c.1184-15098C>A		intron_variant	Intron 10 of 10		NP_001171070.1
SUCLG2	XM_047449140.1	c.1040-7C>A		splice_region_variant, intron_variant	Intron 10 of 10		XP_047305096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLG2	ENST00000307227.10	c.1184-7C>A		splice_region_variant, intron_variant	Intron 10 of 10	1	NM_003848.4	ENSP00000307432.5
SUCLG2	ENST00000493112.5	c.1184-15098C>A		intron_variant	Intron 10 of 10	1		ENSP00000419325.1
SUCLG2	ENST00000460567.5	c.455-7C>A		splice_region_variant, intron_variant	Intron 4 of 4	1		ENSP00000417260.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245600 Hom.: 0 AF XY: 0.00000752 AC XY: 1 AN XY: 133060

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000336

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459536 Hom.: 0 Cov.: 36 AF XY: 0.00000413 AC XY: 3 AN XY: 725758

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000584

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.53

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;