10-86960116-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330120.2(SNCG):ā€‹c.331G>Cā€‹(p.Gly111Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 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: š‘“ 0.0000066 ( 0 hom., cov: 33)

Consequence

SNCG
NM_001330120.2 missense

Scores

2
3
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.520
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.083024204).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNCGNM_003087.3 linkc.279G>C p.Gly93Gly synonymous_variant Exon 3 of 5 ENST00000372017.4 NP_003078.2 O76070Q6FHG5
SNCGNM_001330120.2 linkc.331G>C p.Gly111Arg missense_variant Exon 5 of 7 NP_001317049.1 O76070F8W754
SNCGXM_047425681.1 linkc.606G>C p.Gly202Gly synonymous_variant Exon 5 of 7 XP_047281637.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNCGENST00000372017.4 linkc.279G>C p.Gly93Gly synonymous_variant Exon 3 of 5 1 NM_003087.3 ENSP00000361087.3 O76070

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152048
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248352
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134596
show subpopulations
Gnomad AFR exome
AF:
0.0000623
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152048
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74256
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.071
D
BayesDel_noAF
Uncertain
0.050
CADD
Benign
5.8
DANN
Benign
0.89
DEOGEN2
Benign
0.0098
T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.050
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.083
T
MetaSVM
Uncertain
-0.090
T
PROVEAN
Benign
-0.75
N
REVEL
Benign
0.21
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Vest4
0.12
MutPred
0.35
Gain of MoRF binding (P = 0.014);
MVP
0.37
ClinPred
0.076
T
GERP RS
-4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

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

Other links and lift over

dbSNP: rs111800178; hg19: chr10-88719873; API