rs9864

chr10-86962641-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003087.3(SNCG):c.329A>T(p.Glu110Val) variant causes a missense 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. 14/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.22 (3812 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42622 hom.)
• Consequence: SNCG NM_003087.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.880

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045140684).
• 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	UniProt
SNCG	NM_003087.3	c.329A>T	p.Glu110Val	missense_variant	4/5	ENST00000372017.4
SNCG	NM_001330120.2	c.381A>T	p.Ter127CysextTer28	stop_lost	6/7
SNCG	XM_047425681.1	c.656A>T	p.Glu219Val	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNCG	ENST00000372017.4	c.329A>T	p.Glu110Val	missense_variant	4/5	1	NM_003087.3	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33344 AN: 151822 Hom.: 3815 Cov.: 32

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

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.: 32 AF XY: 0.240 AC XY: 174088 AN XY: 725308

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.: 32 AF XY: 0.217 AC XY: 16138 AN XY: 74250

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	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	17
Dann	Benign	0.86
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.056
Sift	Benign	0.14	T
Sift4G	Benign	0.23	T
Polyphen		0.17	B
Vest4		0.17
MPC		0.15
ClinPred		0.0085	T
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

Other links and lift over

dbSNP: rs9864; hg19: chr10-88722398; COSMIC: COSV62317993; COSMIC: COSV62317993;