rs902321

Variant names:

• chr3-67360742-A-G
• rs902321
• ENST00000493112.5:c.1210T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-67360742-A-G
• chr3-67360742-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001177599.2(SUCLG2):​c.1210T>C​(p.Tyr404His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,522,522 control chromosomes in the GnomAD database, including 117,134 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12309 hom., cov: 32)
  • Exomes 𝑓: 0.39 (104825 hom.)
• Consequence: SUCLG2 NM_001177599.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.25
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.7676773E-4).
• BP6: Variant 3-67360742-A-G is Benign according to our data. Variant chr3-67360742-A-G is described in ClinVar as Benign. ClinVar VariationId is 257599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177599.2. 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_001177599.2		c.1210T>C	p.Tyr404His	missense	Exon 11 of 11	NP_001171070.1	Q96I99-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG2	ENST00000493112.5	TSL:1	c.1210T>C	p.Tyr404His	missense	Exon 11 of 11	ENSP00000419325.1	Q96I99-2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60979 AN: 151840 Hom.: 12302 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.367

GnomAD2 exomes AF: 0.378 AC: 48097 AN: 127338 AF XY: 0.374

Gnomad AFR exome AF: 0.433

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.467

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.397

Gnomad OTH exome AF: 0.363

GnomAD4 exome AF: 0.389 AC: 532905 AN: 1370566 Hom.: 104825 Cov.: 31 AF XY: 0.386 AC XY: 260578 AN XY: 675806

African (AFR) AF: 0.437 AC: 13593 AN: 31092

American (AMR) AF: 0.334 AC: 11192 AN: 33480

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 8611 AN: 24814

East Asian (EAS) AF: 0.449 AC: 15985 AN: 35598

South Asian (SAS) AF: 0.310 AC: 23671 AN: 76438

European-Finnish (FIN) AF: 0.467 AC: 15715 AN: 33626

Middle Eastern (MID) AF: 0.311 AC: 1757 AN: 5646

European-Non Finnish (NFE) AF: 0.392 AC: 420316 AN: 1072486

Other (OTH) AF: 0.385 AC: 22065 AN: 57386

GnomAD4 genome AF: 0.402 AC: 61028 AN: 151956 Hom.: 12309 Cov.: 32 AF XY: 0.400 AC XY: 29716 AN XY: 74248

African (AFR) AF: 0.432 AC: 17919 AN: 41432

American (AMR) AF: 0.324 AC: 4946 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1207 AN: 3472

East Asian (EAS) AF: 0.451 AC: 2329 AN: 5166

South Asian (SAS) AF: 0.300 AC: 1441 AN: 4806

European-Finnish (FIN) AF: 0.460 AC: 4848 AN: 10538

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26962 AN: 67958

Other (OTH) AF: 0.372 AC: 786 AN: 2112

Alfa AF: 0.397 Hom.: 37823

Bravo AF: 0.396

TwinsUK AF: 0.383 AC: 1419

ALSPAC AF: 0.381 AC: 1469

ExAC AF: 0.312 AC: 4449

Asia WGS AF: 0.419 AC: 1456 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.6
DANN	Benign	0.66
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.00078	T
MetaSVM	Benign	-0.96	T
PhyloP100		1.3
PROVEAN	Benign	0.20	N
REVEL	Benign	0.081
Sift	Benign	0.18	T
Sift4G	Benign	0.60	T
Vest4		0.072
MPC		0.065
ClinPred		0.0013	T
GERP RS		3.2
gMVP		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs902321; hg19: chr3-67411166; COSMIC: COSV72330715;