10-86960032-C-G

Variant names:

• chr10-86960032-C-G
• rs760113
• NM_003087.3:c.195C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330120.2(SNCG):​c.247C>G​(p.Arg83Gly) variant causes a missense 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. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R83H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.24 (4712 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43349 hom.)
• Consequence: SNCG NM_001330120.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 22 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011928678).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330120.2. 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
	SNCG	NM_003087.3	MANE Select	c.195C>G	p.Ala65Ala	synonymous	Exon 3 of 5	NP_003078.2	O76070
	SNCG	NM_001330120.2		c.247C>G	p.Arg83Gly	missense	Exon 5 of 7	NP_001317049.1	F8W754

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCG	ENST00000372017.4	TSL:1 MANE Select	c.195C>G	p.Ala65Ala	synonymous	Exon 3 of 5	ENSP00000361087.3	O76070
	SNCG	ENST00000348795.8	TSL:2	c.247C>G	p.Arg83Gly	missense	Exon 3 of 5	ENSP00000344658.4	F8W754
	SNCG	ENST00000930521.1		c.195C>G	p.Ala65Ala	synonymous	Exon 4 of 6	ENSP00000600580.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37144 AN: 151984 Hom.: 4710 Cov.: 32

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

GnomAD2 exomes AF: 0.228 AC: 55013 AN: 240970 AF XY: 0.233

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 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.: 35 AF XY: 0.242 AC XY: 175517 AN XY: 724198

African (AFR) AF: 0.268 AC: 8971 AN: 33456

American (AMR) AF: 0.199 AC: 8765 AN: 44066

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5886 AN: 25946

East Asian (EAS) AF: 0.0771 AC: 3050 AN: 39540

South Asian (SAS) AF: 0.297 AC: 25249 AN: 84942

European-Finnish (FIN) AF: 0.198 AC: 10422 AN: 52660

Middle Eastern (MID) AF: 0.210 AC: 1209 AN: 5758

European-Non Finnish (NFE) AF: 0.246 AC: 272938 AN: 1110230

Other (OTH) AF: 0.239 AC: 14402 AN: 60220

GnomAD4 genome AF: 0.244 AC: 37162 AN: 152104 Hom.: 4712 Cov.: 32 AF XY: 0.242 AC XY: 17961 AN XY: 74334

African (AFR) AF: 0.279 AC: 11566 AN: 41502

American (AMR) AF: 0.225 AC: 3435 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 795 AN: 3470

East Asian (EAS) AF: 0.0720 AC: 372 AN: 5168

South Asian (SAS) AF: 0.310 AC: 1493 AN: 4816

European-Finnish (FIN) AF: 0.190 AC: 2013 AN: 10586

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16728 AN: 67954

Other (OTH) AF: 0.240 AC: 507 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Uncertain	0.010
CADD	Benign	0.21
DANN	Benign	0.85
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.92	T
PhyloP100		-1.4
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.077	T
Vest4		0.081
ClinPred		0.013	T
GERP RS		-8.2
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs760113; hg19: chr10-88719789; COSMIC: COSV62318168; COSMIC: COSV62318168;