Genetic Variant SUCLG2:p.Arg381Gln (chr3-67400772-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003848.4(SUCLG2):c.1142G>A(p.Arg381Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,611,900 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R381W) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 2 hom. )

Consequence

SUCLG2
NM_003848.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.45

Publications

2 publications found

Variant links:

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]

SUCLG2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011443377).

BP6

Variant 3-67400772-C-T is Benign according to our data. Variant chr3-67400772-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2080642.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG2	NM_003848.4	MANE Select	c.1142G>A	p.Arg381Gln	missense	Exon 10 of 11	NP_003839.2	Q96I99-1
	SUCLG2	NM_001177599.2		c.1142G>A	p.Arg381Gln	missense	Exon 10 of 11	NP_001171070.1	Q96I99-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUCLG2	ENST00000307227.10	TSL:1 MANE Select	c.1142G>A	p.Arg381Gln	missense	Exon 10 of 11	ENSP00000307432.5	Q96I99-1
SUCLG2	ENST00000493112.5	TSL:1	c.1142G>A	p.Arg381Gln	missense	Exon 10 of 11	ENSP00000419325.1	Q96I99-2
SUCLG2	ENST00000460567.5	TSL:1	c.413G>A	p.Arg138Gln	missense	Exon 4 of 5	ENSP00000417260.1	H0Y852

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000459

AC:

114

AN:

248512

AF XY:

0.000571

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000260

AC:

380

AN:

1459646

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

258

AN XY:

726196

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33370

American (AMR)

AF:

0.0000450

AC:

AN:

44442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.00281

AC:

242

AN:

86074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000444

AC:

AN:

4502

European-Non Finnish (NFE)

AF:

0.0000989

AC:

110

AN:

1111872

Other (OTH)

AF:

0.000382

AC:

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000177

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41532

American (AMR)

AF:

0.0000654

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00352

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000350

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.000505

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.099

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

M_CAP

Benign

0.0062

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.85

PhyloP100

1.4

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

REVEL

Benign

0.076

Sift

Benign

0.29

Sift4G

Benign

0.20

Polyphen

0.0050

Vest4

0.22

MVP

0.70

MPC

0.058

ClinPred

0.019

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.61

Mutation Taster

=68/32

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over