rs74675534

Positions:

• chr3-67529111-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003848.4(SUCLG2):​c.302A>G​(p.Lys101Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00778 in 1,612,796 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (66 hom.)
• Consequence: SUCLG2 NM_003848.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.99

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019182414).
• BP6: Variant 3-67529111-T-C is Benign according to our data. Variant chr3-67529111-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 257601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCLG2	NM_003848.4	c.302A>G	p.Lys101Arg	missense_variant	3/11	ENST00000307227.10	NP_003839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUCLG2	ENST00000307227.10	c.302A>G	p.Lys101Arg	missense_variant	3/11	1	NM_003848.4	ENSP00000307432	P1
SUCLG2	ENST00000493112.5	c.302A>G	p.Lys101Arg	missense_variant	3/11	1		ENSP00000419325
SUCLG2	ENST00000492795.1	c.302A>G	p.Lys101Arg	missense_variant	3/10	2		ENSP00000417589

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 733 AN: 152128 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00861

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00482 AC: 1198 AN: 248596 Hom.: 7 AF XY: 0.00497 AC XY: 670 AN XY: 134852

Gnomad AFR exome AF: 0.00149

Gnomad AMR exome AF: 0.00172

Gnomad ASJ exome AF: 0.00777

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00247

Gnomad FIN exome AF: 0.00149

Gnomad NFE exome AF: 0.00797

Gnomad OTH exome AF: 0.00514

GnomAD4 exome AF: 0.00809 AC: 11820 AN: 1460550 Hom.: 66 Cov.: 30 AF XY: 0.00788 AC XY: 5726 AN XY: 726532

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.00697

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00238

Gnomad4 FIN exome AF: 0.00195

Gnomad4 NFE exome AF: 0.00970

Gnomad4 OTH exome AF: 0.00719

GnomAD4 genome AF: 0.00481 AC: 733 AN: 152246 Hom.: 2 Cov.: 32 AF XY: 0.00390 AC XY: 290 AN XY: 74434

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00923

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.00862

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00807 Hom.: 4

Bravo AF: 0.00489

TwinsUK AF: 0.0108 AC: 40

ALSPAC AF: 0.00986 AC: 38

ESP6500AA AF: 0.00163 AC: 6

ESP6500EA AF: 0.0105 AC: 86

ExAC AF: 0.00475 AC: 574

Asia WGS AF: 0.00144 AC: 5 AN: 3476

EpiCase AF: 0.00857

EpiControl AF: 0.00968

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	.;T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D
MetaRNN	Benign	0.019	T;T;T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.4	M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Uncertain	0.46
Sift	Benign	0.034	D;D;D
Sift4G	Uncertain	0.025	D;D;D
Polyphen		0.14	.;B;.
Vest4		0.56
MVP		0.73
MPC		0.075
ClinPred		0.050	T
GERP RS		5.0
Varity_R		0.40
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs74675534; hg19: chr3-67579535; COSMIC: COSV56203928; COSMIC: COSV56203928;