NM_003848.4:c.302A>G

Variant names:

• chr3-67529111-T-C
• rs74675534
• NM_003848.4:c.302A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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 -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 Benign/Likely_benign. ClinVar VariationId is 257601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003848.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG2	NM_003848.4	MANE Select	c.302A>G	p.Lys101Arg	missense	Exon 3 of 11	NP_003839.2
	SUCLG2	NM_001177599.2		c.302A>G	p.Lys101Arg	missense	Exon 3 of 11	NP_001171070.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG2	ENST00000307227.10	TSL:1 MANE Select	c.302A>G	p.Lys101Arg	missense	Exon 3 of 11	ENSP00000307432.5
	SUCLG2	ENST00000493112.5	TSL:1	c.302A>G	p.Lys101Arg	missense	Exon 3 of 11	ENSP00000419325.1
	SUCLG2	ENST00000951870.1		c.302A>G	p.Lys101Arg	missense	Exon 3 of 11	ENSP00000621929.1

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

GnomAD2 exomes AF: 0.00482 AC: 1198 AN: 248596 AF XY: 0.00497

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 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

African (AFR) AF: 0.00111 AC: 37 AN: 33416

American (AMR) AF: 0.00152 AC: 68 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.00697 AC: 182 AN: 26112

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.00238 AC: 205 AN: 85992

European-Finnish (FIN) AF: 0.00195 AC: 104 AN: 53410

Middle Eastern (MID) AF: 0.00150 AC: 8 AN: 5334

European-Non Finnish (NFE) AF: 0.00970 AC: 10781 AN: 1111666

Other (OTH) AF: 0.00719 AC: 434 AN: 60326

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

African (AFR) AF: 0.00156 AC: 65 AN: 41550

American (AMR) AF: 0.00170 AC: 26 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 32 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00862 AC: 586 AN: 68016

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00741 Hom.: 5

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

ClinVar submissions as Germline

Significance: Benign/Likely 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	0.10
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
MetaRNN	Benign	0.019	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.46
Sift	Benign	0.034	D
Sift4G	Uncertain	0.025	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
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs74675534; hg19: chr3-67579535; COSMIC: COSV56203928; COSMIC: COSV56203928;