Genetic Variant NM_003087.3:c.195C>G (chr10-86960032-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003087.3(SNCG):c.195C>G(p.Ala65Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,608,922 control chromosomes in the GnomAD database, including 48,061 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 0.24 ( 4712 hom., cov: 32)

Exomes 𝑓: 0.24 ( 43349 hom. )

Consequence

SNCG
NM_003087.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011928678).

BP7

Synonymous conserved (PhyloP=-1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCG	NM_003087.3 link	c.195C>G	p.Ala65Ala	synonymous_variant	Exon 3 of 5	ENST00000372017.4	NP_003078.2	O76070Q6FHG5
SNCG	NM_001330120.2 link	c.247C>G	p.Arg83Gly	missense_variant	Exon 5 of 7		NP_001317049.1	O76070F8W754
SNCG	XM_047425681.1 link	c.522C>G	p.Ala174Ala	synonymous_variant	Exon 5 of 7		XP_047281637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCG	ENST00000372017.4 link	c.195C>G	p.Ala65Ala	synonymous_variant	Exon 3 of 5	1	NM_003087.3	ENSP00000361087.3		O76070

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37144

AN:

151984

Hom.:

4710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.0715

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.242

GnomAD3 exomes

AF:

0.228

AC:

55013

AN:

240970

Hom.:

6655

AF XY:

0.233

AC XY:

30334

AN XY:

130330

show subpopulations

Gnomad AFR exome

AF:

0.274

Gnomad AMR exome

AF:

0.200

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.0756

Gnomad SAS exome

AF:

0.301

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.241

AC:

350892

AN:

1456818

Hom.:

43349

Cov.:

AF XY:

0.242

AC XY:

175517

AN XY:

724198

show subpopulations

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.199

Gnomad4 ASJ exome

AF:

0.227

Gnomad4 EAS exome

AF:

0.0771

Gnomad4 SAS exome

AF:

0.297

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.246

Gnomad4 OTH exome

AF:

0.239

GnomAD4 genome

AF:

0.244

AC:

37162

AN:

152104

Hom.:

4712

Cov.:

AF XY:

0.242

AC XY:

17961

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.229

Gnomad4 EAS

AF:

0.0720

Gnomad4 SAS

AF:

0.310

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.246

Gnomad4 OTH

AF:

0.240

Alfa

AF:

0.204

Hom.:

1135

Bravo

AF:

0.243

TwinsUK

AF:

0.268

AC:

994

ALSPAC

AF:

0.257

AC:

992

ESP6500AA

AF:

0.274

AC:

1208

ESP6500EA

AF:

0.249

AC:

2140

ExAC

AF:

0.230

AC:

27903

Asia WGS

AF:

0.235

AC:

815

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Uncertain

0.010

CADD

Benign

0.21

DANN

Benign

0.85

DEOGEN2

Benign

0.0068

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0012

MetaSVM

Benign

-0.92

PROVEAN

Benign

-0.19

REVEL

Benign

0.23

Sift

Pathogenic

0.0

Sift4G

Benign

0.077

Vest4

0.081

ClinPred

0.013

GERP RS

-8.2

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

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