Variant 10-86962641-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4BA1

The NM_001330120.2(SNCG):c.381A>T(p.Ter127Cysext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,610,028 control chromosomes in the GnomAD database, including 46,434 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 3812 hom., cov: 32)

Exomes 𝑓: 0.24 ( 42622 hom. )

Consequence

SNCG
NM_001330120.2 stop_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.880

Variant links:

Genes affected

SNCG (HGNC:11141): (synuclein gamma) This gene encodes a member of the synuclein family of proteins which are believed to be involved in the pathogenesis of neurodegenerative diseases. Mutations in this gene have also been associated with breast tumor development. [provided by RefSeq, Jan 2010]

SNCG links:

MMRN2 (HGNC:19888): (multimerin 2) This gene encodes a protein belonging to the member of elastin microfibril interface-located (EMILIN) protein family. This family member is an extracellular matrix glycoprotein that can interfere with tumor angiogenesis and growth. It serves as a transforming growth factor beta antagonist and can interfere with the VEGF-A/VEGFR2 pathway. A related pseudogene has been identified on chromosome 6. [provided by RefSeq, Aug 2012]

MMRN2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM4

Stoplost variant in NM_001330120.2 Downstream stopcodon found after 227 codons.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCG	NM_003087.3 link	c.329A>T	p.Glu110Val	missense_variant	4/5	ENST00000372017.4	NP_003078.2	O76070Q6FHG5
SNCG	NM_001330120.2 link	c.381A>T	p.Ter127Cysext*?	stop_lost	6/7		NP_001317049.1	O76070F8W754
SNCG	XM_047425681.1 link	c.656A>T	p.Glu219Val	missense_variant	6/7		XP_047281637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCG	ENST00000372017.4 link	c.329A>T	p.Glu110Val	missense_variant	4/5	1	NM_003087.3	ENSP00000361087.3		O76070

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33344

AN:

151822

Hom.:

3815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.0720

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.224

GnomAD3 exomes

AF:

0.221

AC:

54619

AN:

247426

Hom.:

6456

AF XY:

0.227

AC XY:

30387

AN XY:

133918

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.0756

Gnomad SAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.241

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.238

AC:

347188

AN:

1458088

Hom.:

42622

Cov.:

AF XY:

0.240

AC XY:

174088

AN XY:

725308

show subpopulations

Gnomad4 AFR exome

AF:

0.181

Gnomad4 AMR exome

AF:

0.193

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.0769

Gnomad4 SAS exome

AF:

0.297

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.219

AC:

33338

AN:

151940

Hom.:

3812

Cov.:

AF XY:

0.217

AC XY:

16138

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.0726

Gnomad4 SAS

AF:

0.311

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.222

Alfa

AF:

0.235

Hom.:

1414

Bravo

AF:

0.215

TwinsUK

AF:

0.268

AC:

993

ALSPAC

AF:

0.257

AC:

989

ESP6500AA

AF:

0.187

AC:

824

ESP6500EA

AF:

0.249

AC:

2144

ExAC

AF:

0.225

AC:

27250

Asia WGS

AF:

0.227

AC:

789

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.30

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.7

REVEL

Benign

0.056

Sift

Benign

0.14

Sift4G

Benign

0.23

Polyphen

0.17

Vest4

0.17

MPC

0.15

ClinPred

0.0085

GERP RS

2.6

Varity_R

0.080

gMVP

0.35

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over