10-86960094-A-G

Variant summary

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

The NM_003087.3(SNCG):ā€‹c.257A>Gā€‹(p.Glu86Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,612,998 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 33)
Exomes š‘“: 0.000049 ( 1 hom. )

Consequence

SNCG
NM_003087.3 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.08
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 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.257A>G p.Glu86Gly missense_variant Exon 3 of 5 ENST00000372017.4 NP_003078.2 O76070Q6FHG5
SNCGXM_047425681.1 linkc.584A>G p.Glu195Gly missense_variant Exon 5 of 7 XP_047281637.1
SNCGNM_001330120.2 linkc.309A>G p.Gly103Gly synonymous_variant Exon 5 of 7 NP_001317049.1 O76070F8W754

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNCGENST00000372017.4 linkc.257A>G p.Glu86Gly missense_variant Exon 3 of 5 1 NM_003087.3 ENSP00000361087.3 O76070

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151884
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00135
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:
0.0000642
AC:
16
AN:
249406
Hom.:
0
AF XY:
0.0000518
AC XY:
7
AN XY:
135086
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000871
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
AF:
0.0000493
AC:
72
AN:
1461114
Hom.:
1
Cov.:
33
AF XY:
0.0000440
AC XY:
32
AN XY:
726892
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00179
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000461
AC:
7
AN:
151884
Hom.:
0
Cov.:
33
AF XY:
0.0000674
AC XY:
5
AN XY:
74148
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00135
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000907
ExAC
AF:
0.0000824
AC:
10
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.257A>G (p.E86G) alteration is located in exon 3 (coding exon 3) of the SNCG gene. This alteration results from a A to G substitution at nucleotide position 257, causing the glutamic acid (E) at amino acid position 86 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.013
T
BayesDel_noAF
Pathogenic
0.15
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.81
T
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.52
D
MetaSVM
Uncertain
0.15
D
MutationAssessor
Benign
1.5
L
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-2.1
N
REVEL
Pathogenic
0.70
Sift
Benign
0.75
T
Sift4G
Benign
0.80
T
Polyphen
1.0
D
Vest4
0.81
MVP
0.83
MPC
0.63
ClinPred
0.23
T
GERP RS
4.7
Varity_R
0.27
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs755430015; hg19: chr10-88719851; API