Variant 3-67400773-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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.

Frequency

Genomes: 𝑓 0.054 ( 691 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 640 hom. )

Consequence

SUCLG2
NM_003848.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
SUCLG2	NM_003848.4 linkuse as main transcript	c.1141C>T	p.Arg381Trp	missense_variant	10/11	ENST00000307227.10	NP_003839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUCLG2	ENST00000307227.10 linkuse as main transcript	c.1141C>T	p.Arg381Trp	missense_variant	10/11	1	NM_003848.4	ENSP00000307432	P1	Q96I99-1
SUCLG2	ENST00000493112.5 linkuse as main transcript	c.1141C>T	p.Arg381Trp	missense_variant	10/11	1		ENSP00000419325		Q96I99-2
SUCLG2	ENST00000460567.5 linkuse as main transcript	c.415C>T	p.Arg139Trp	missense_variant	4/5	1		ENSP00000417260

Frequencies

GnomAD3 genomes

AF:

0.0535

AC:

8131

AN:

152066

Hom.:

688

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00494

AC XY:

3587

AN XY:

726190

show subpopulations

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.:

AF XY:

0.0527

AC XY:

3920

AN XY:

74390

show subpopulations

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:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.173

AC:

674

ESP6500EA

AF:

0.000724

AC:

ExAC

AF:

0.0160

AC:

1935

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000982

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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

0.27

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

.;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

M;M

MutationTaster

Benign

0.000054

P;P

PrimateAI

Benign

0.37

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

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

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