rs1800373

Variant names:

• chr10-86958679-A-C
• rs1800373
• NM_003087.3:c.-19A>C

Variant summary

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

The NM_003087.3(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 NM_003087.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• 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 (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 rank	MANE	Protein	UniProt
SNCG	NM_003087.3	c.-19A>C		5_prime_UTR_variant	Exon 1 of 5	ENST00000372017.4	NP_003078.2
SNCG	XM_047425681.1	c.309A>C	p.Ala103Ala	synonymous_variant	Exon 3 of 7		XP_047281637.1
SNCG	NM_001330120.2	c.-19A>C		5_prime_UTR_variant	Exon 3 of 7		NP_001317049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCG	ENST00000372017.4	c.-19A>C		5_prime_UTR_variant	Exon 1 of 5	1	NM_003087.3	ENSP00000361087.3

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

GnomAD2 exomes AF: 0.537 AC: 133914 AN: 249400 AF XY: 0.535

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 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

African (AFR) AF: 0.520 AC: 17403 AN: 33450

American (AMR) AF: 0.499 AC: 22279 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 14198 AN: 26110

East Asian (EAS) AF: 0.693 AC: 27503 AN: 39674

South Asian (SAS) AF: 0.458 AC: 39488 AN: 86188

European-Finnish (FIN) AF: 0.584 AC: 31088 AN: 53256

Middle Eastern (MID) AF: 0.551 AC: 3096 AN: 5618

European-Non Finnish (NFE) AF: 0.543 AC: 603532 AN: 1111618

Other (OTH) AF: 0.547 AC: 32982 AN: 60340

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

African (AFR) AF: 0.512 AC: 21248 AN: 41540

American (AMR) AF: 0.524 AC: 8017 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1886 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3620 AN: 5162

South Asian (SAS) AF: 0.449 AC: 2165 AN: 4822

European-Finnish (FIN) AF: 0.587 AC: 6212 AN: 10576

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.541 AC: 36762 AN: 67998

Other (OTH) AF: 0.559 AC: 1182 AN: 2116

Alfa AF: 0.540 Hom.: 18953

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
PhyloP100		0.028
PromoterAI		-0.064	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800373; hg19: chr10-88718436;