Variant 4-89724523-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000345.4(SNCA):c.*2105G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,694 control chromosomes in the GnomAD database, including 7,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 7218 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

SNCA
NM_000345.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0930

Variant links:

Genes affected

SNCA (HGNC:11138): (synuclein alpha) Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimer's disease. Alternatively spliced transcripts encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2016]

SNCA links:

SNCA (HGNC:):

SNCA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 4-89724523-C-T is Benign according to our data. Variant chr4-89724523-C-T is described in ClinVar as [Benign]. Clinvar id is 350064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCA	NM_000345.4 linkuse as main transcript	c.*2105G>A		3_prime_UTR_variant	6/6	ENST00000394991.8	NP_000336.1	P37840-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCA	ENST00000394991.8 linkuse as main transcript	c.*2105G>A		3_prime_UTR_variant	6/6	1	NM_000345.4	ENSP00000378442.4		P37840-1

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35785

AN:

151578

Hom.:

7203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.514

Gnomad AMI

AF:

0.0714

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.530

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.0700

Gnomad OTH

AF:

0.224

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.236

AC:

35842

AN:

151694

Hom.:

7218

Cov.:

AF XY:

0.239

AC XY:

17753

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.514

Gnomad4 AMR

AF:

0.246

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.529

Gnomad4 SAS

AF:

0.270

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.0700

Gnomad4 OTH

AF:

0.227

Alfa

AF:

0.156

Hom.:

533

Bravo

AF:

0.264

Asia WGS

AF:

0.427

AC:

1481

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Parkinson Disease, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.6

DANN

Benign

0.27

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over