NM_003848.4:c.1186A>T

Variant names:

• chr3-67375857-T-A
• NM_003848.4:c.1186A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003848.4(SUCLG2):​c.1186A>T​(p.Thr396Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,460,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 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: 6.8e-7 (0 hom.)
• Consequence: SUCLG2 NM_003848.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.19

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLG2	NM_003848.4	c.1186A>T	p.Thr396Ser	missense_variant, splice_region_variant	Exon 11 of 11	ENST00000307227.10	NP_003839.2
SUCLG2	XM_047449140.1	c.1042A>T	p.Thr348Ser	missense_variant, splice_region_variant	Exon 11 of 11		XP_047305096.1
SUCLG2	XM_017007420.3	c.*605A>T		3_prime_UTR_variant	Exon 11 of 11		XP_016862909.1
SUCLG2	NM_001177599.2	c.1184-15089A>T		intron_variant	Intron 10 of 10		NP_001171070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLG2	ENST00000307227.10	c.1186A>T	p.Thr396Ser	missense_variant, splice_region_variant	Exon 11 of 11	1	NM_003848.4	ENSP00000307432.5
SUCLG2	ENST00000460567.5	c.457A>T	p.Thr153Ser	missense_variant, splice_region_variant	Exon 5 of 5	1		ENSP00000417260.1
SUCLG2	ENST00000493112.5	c.1184-15089A>T		intron_variant	Intron 10 of 10	1		ENSP00000419325.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460662 Hom.: 0 Cov.: 40 AF XY: 0.00000138 AC XY: 1 AN XY: 726466

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.8	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.017	D
Polyphen		0.42	B
Vest4		0.58
MutPred		0.78		Loss of catalytic residue at T396 (P = 0.0312);
MVP		0.90
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-67426281;