3-67400773-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003848.4(SUCLG2):c.1141C>T(p.Arg381Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,611,788 control chromosomes in the GnomAD database, including 1,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R381Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.054 (691 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (640 hom.)
• Consequence: SUCLG2 NM_003848.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.02

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001975894).
• BP6: Variant 3-67400773-G-A is Benign according to our data. Variant chr3-67400773-G-A is described in ClinVar as [Benign]. Clinvar id is 257598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUCLG2	NM_003848.4	c.1141C>T	p.Arg381Trp	missense_variant	10/11	ENST00000307227.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUCLG2	ENST00000307227.10	c.1141C>T	p.Arg381Trp	missense_variant	10/11	1	NM_003848.4	P1
SUCLG2	ENST00000493112.5	c.1141C>T	p.Arg381Trp	missense_variant	10/11	1
SUCLG2	ENST00000460567.5	c.415C>T	p.Arg139Trp	missense_variant	4/5	1

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8131 AN: 152066 Hom.: 688 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0455

GnomAD3 exomes AF: 0.0134 AC: 3336 AN: 248414 Hom.: 284 AF XY: 0.0102 AC XY: 1375 AN XY: 134870

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.00800

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000263

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000717

Gnomad OTH exome AF: 0.00747

GnomAD4 exome AF: 0.00561 AC: 8184 AN: 1459604 Hom.: 640 Cov.: 31 AF XY: 0.00494 AC XY: 3587 AN XY: 726190

Gnomad4 AFR exome AF: 0.189

Gnomad4 AMR exome AF: 0.0100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000511

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000505

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.0535 AC: 8143 AN: 152184 Hom.: 691 Cov.: 32 AF XY: 0.0527 AC XY: 3920 AN XY: 74390

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0221

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0451

Alfa AF: 0.00950 Hom.: 184

Bravo AF: 0.0616

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.173 AC: 674

ESP6500EA AF: 0.000724 AC: 6

ExAC AF: 0.0160 AC: 1935

Asia WGS AF: 0.0120 AC: 40 AN: 3478

EpiCase AF: 0.000982

EpiControl AF: 0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.24
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T;T
MetaRNN	Benign	0.0020	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M;M
MutationTaster	Benign	0.000054	P;P
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Benign	0.22
Sift	Benign	0.057	T;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.032	.;B
Vest4		0.18
MPC		0.055
ClinPred		0.075	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs7623258; hg19: chr3-67451197; COSMIC: COSV56214570;