10-86962661-G-T

Variant summary

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

The NM_003087.3(SNCG):​c.349G>T​(p.Glu117*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

SNCG
NM_003087.3 stop_gained

Scores

2
2
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNCGNM_003087.3 linkc.349G>T p.Glu117* stop_gained Exon 4 of 5 ENST00000372017.4 NP_003078.2 O76070Q6FHG5
SNCGXM_047425681.1 linkc.676G>T p.Glu226* stop_gained Exon 6 of 7 XP_047281637.1
SNCGNM_001330120.2 linkc.*20G>T 3_prime_UTR_variant Exon 6 of 7 NP_001317049.1 O76070F8W754

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNCGENST00000372017.4 linkc.349G>T p.Glu117* stop_gained Exon 4 of 5 1 NM_003087.3 ENSP00000361087.3 O76070

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.42
D
BayesDel_noAF
Pathogenic
0.36
CADD
Pathogenic
51
DANN
Uncertain
1.0
Eigen
Uncertain
0.50
Eigen_PC
Benign
0.21
FATHMM_MKL
Benign
0.61
D
Vest4
0.41
GERP RS
2.9

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.84
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.84
Position offset: -2
DS_DL_spliceai
0.51
Position offset: 14

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs779800178; hg19: chr10-88722418; API