rs1800373

Positions:

• chr10-86958679-A-C

Variant summary

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

The ENST00000372017.4(SNCG):​c.-19A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 1,613,038 control chromosomes in the GnomAD database, including 238,022 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 0.54 (22094 hom., cov: 34)
  • Exomes 𝑓: 0.54 (215928 hom.)
• Consequence: SNCG ENST00000372017.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

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 (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCG	NM_003087.3	c.-19A>C		5_prime_UTR_variant	1/5	ENST00000372017.4	NP_003078.2
SNCG	XM_047425681.1	c.309A>C	p.Ala103=	synonymous_variant	3/7		XP_047281637.1
SNCG	NM_001330120.2	c.-19A>C		5_prime_UTR_variant	3/7		NP_001317049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCG	ENST00000372017.4	c.-19A>C		5_prime_UTR_variant	1/5	1	NM_003087.3	ENSP00000361087	P1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81690 AN: 152056 Hom.: 22078 Cov.: 34

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.557

GnomAD3 exomes AF: 0.537 AC: 133914 AN: 249400 Hom.: 36465 AF XY: 0.535 AC XY: 72209 AN XY: 134986

Gnomad AFR exome AF: 0.512

Gnomad AMR exome AF: 0.492

Gnomad ASJ exome AF: 0.539

Gnomad EAS exome AF: 0.692

Gnomad SAS exome AF: 0.455

Gnomad FIN exome AF: 0.587

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.532

GnomAD4 exome AF: 0.542 AC: 791569 AN: 1460864 Hom.: 215928 Cov.: 57 AF XY: 0.539 AC XY: 391831 AN XY: 726728

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.499

Gnomad4 ASJ exome AF: 0.544

Gnomad4 EAS exome AF: 0.693

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.584

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.547

GnomAD4 genome AF: 0.537 AC: 81748 AN: 152174 Hom.: 22094 Cov.: 34 AF XY: 0.538 AC XY: 40012 AN XY: 74396

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.559

Alfa AF: 0.540 Hom.: 16907

Bravo AF: 0.537

Asia WGS AF: 0.555 AC: 1932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.0
DANN	Benign	0.86

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: rs1800373; hg19: chr10-88718436;