Variant 3-67375857-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003848.4(SUCLG2):c.1186A>G(p.Thr396Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.104 in 1,612,796 control chromosomes in the GnomAD database, including 9,536 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.088 ( 693 hom., cov: 33)

Exomes 𝑓: 0.11 ( 8843 hom. )

Consequence

SUCLG2
NM_003848.4 missense, splice_region

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.19

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044909418).

BP6

Variant 3-67375857-T-C is Benign according to our data. Variant chr3-67375857-T-C is described in ClinVar as [Benign]. Clinvar id is 3056708.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUCLG2	NM_003848.4 linkuse as main transcript	c.1186A>G	p.Thr396Ala	missense_variant, splice_region_variant	11/11	ENST00000307227.10	NP_003839.2	Q96I99-1
SUCLG2	XM_047449140.1 linkuse as main transcript	c.1042A>G	p.Thr348Ala	missense_variant, splice_region_variant	11/11		XP_047305096.1
SUCLG2	XM_017007420.3 linkuse as main transcript	c.*605A>G		3_prime_UTR_variant	11/11		XP_016862909.1
SUCLG2	NM_001177599.2 linkuse as main transcript	c.1184-15089A>G		intron_variant			NP_001171070.1	Q96I99-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SUCLG2	ENST00000307227.10 linkuse as main transcript	c.1186A>G	p.Thr396Ala	missense_variant, splice_region_variant	11/11	1	NM_003848.4	ENSP00000307432.5	Q96I99-1
SUCLG2	ENST00000460567.5 linkuse as main transcript	c.457A>G	p.Thr153Ala	missense_variant, splice_region_variant	5/5	1		ENSP00000417260.1	H0Y852
SUCLG2	ENST00000493112.5 linkuse as main transcript	c.1184-15089A>G		intron_variant		1		ENSP00000419325.1	Q96I99-2

Frequencies

GnomAD3 genomes

AF:

0.0878

AC:

13355

AN:

152154

Hom.:

696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0475

Gnomad AMI

AF:

0.0440

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.0416

Gnomad SAS

AF:

0.0539

Gnomad FIN

AF:

0.0400

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.0904

AC:

22369

AN:

247422

Hom.:

1254

AF XY:

0.0925

AC XY:

12398

AN XY:

134082

show subpopulations

Gnomad AFR exome

AF:

0.0455

Gnomad AMR exome

AF:

0.0697

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.0371

Gnomad SAS exome

AF:

0.0567

Gnomad FIN exome

AF:

0.0411

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.105

AC:

153683

AN:

1460524

Hom.:

8843

Cov.:

AF XY:

0.105

AC XY:

76475

AN XY:

726394

show subpopulations

Gnomad4 AFR exome

AF:

0.0457

Gnomad4 AMR exome

AF:

0.0703

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.0340

Gnomad4 SAS exome

AF:

0.0575

Gnomad4 FIN exome

AF:

0.0427

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.0876

AC:

13339

AN:

152272

Hom.:

693

Cov.:

AF XY:

0.0838

AC XY:

6238

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0474

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.0419

Gnomad4 SAS

AF:

0.0541

Gnomad4 FIN

AF:

0.0400

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.126

Alfa

AF:

0.116

Hom.:

1712

Bravo

AF:

0.0918

TwinsUK

AF:

0.120

AC:

444

ALSPAC

AF:

0.125

AC:

480

ESP6500AA

AF:

0.0489

AC:

189

ESP6500EA

AF:

0.120

AC:

995

ExAC

AF:

0.0892

AC:

10779

Asia WGS

AF:

0.0460

AC:

161

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SUCLG2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.6

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-4.0

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.64

Vest4

0.28

ClinPred

0.096

GERP RS

5.4

Varity_R

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over