rs779800178

Variant names:

• chr10-86962661-G-A
• NM_003087.3:c.349G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-86962661-G-A
• chr10-86962661-G-C
• chr10-86962661-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003087.3(SNCG):​c.349G>A​(p.Glu117Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SNCG NM_003087.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1665008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCG	NM_003087.3	c.349G>A	p.Glu117Lys	missense_variant	Exon 4 of 5	ENST00000372017.4	NP_003078.2
SNCG	XM_047425681.1	c.676G>A	p.Glu226Lys	missense_variant	Exon 6 of 7		XP_047281637.1
SNCG	NM_001330120.2	c.*20G>A		3_prime_UTR_variant	Exon 6 of 7		NP_001317049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCG	ENST00000372017.4	c.349G>A	p.Glu117Lys	missense_variant	Exon 4 of 5	1	NM_003087.3	ENSP00000361087.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460352 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726390

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	0.0097	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.17	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.20
Sift	Uncertain	0.014	D
Sift4G	Benign	0.10	T
Polyphen		0.089	B
Vest4		0.19
MutPred		0.60		Gain of ubiquitination at E117 (P = 0.0077);
MVP		0.70
MPC		0.14
ClinPred		0.44	T
GERP RS		2.9
Varity_R		0.12
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-88722418;