Variant 5-176626472-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP5BP4BS2

The NM_003085.5(SNCB):c.208G>A(p.Val70Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,614,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

SNCB
NM_003085.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

SNCB (HGNC:11140): (synuclein beta) This gene encodes a member of a small family of proteins that inhibit phospholipase D2 and may function in neuronal plasticity. The encoded protein is abundant in lesions of patients with Alzheimer disease. A mutation in this gene was found in individuals with dementia with Lewy bodies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

SNCB links:

SNCB (HGNC:):

SNCB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP5

Variant 5-176626472-C-T is Pathogenic according to our data. Variant chr5-176626472-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 7025.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.3383683). . Strength limited to SUPPORTING due to the PP5.

BS2

High AC in GnomAdExome4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCB	NM_003085.5 linkuse as main transcript	c.208G>A	p.Val70Met	missense_variant	4/6	ENST00000393693.7	NP_003076.1	Q16143

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCB	ENST00000393693.7 linkuse as main transcript	c.208G>A	p.Val70Met	missense_variant	4/6	1	NM_003085.5	ENSP00000377296.2		Q16143

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152158

Hom.:

Cov.:

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:

0.000385

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:

0.0000557

AC:

AN:

251404

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000831

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000688

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Lewy body dementia

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 14, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.62

D;T;D;D;D

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.91

.;D;.;.;D

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.34

T;T;T;T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.5

L;.;L;L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.5

N;.;N;N;N

REVEL

Uncertain

0.62

Sift

Benign

0.071

T;.;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T

Polyphen

0.28

B;.;B;B;B

Vest4

0.67

MutPred

0.91

Gain of disorder (P = 0.0886);.;Gain of disorder (P = 0.0886);Gain of disorder (P = 0.0886);Gain of disorder (P = 0.0886);

MVP

0.73

MPC

1.3

ClinPred

0.11

GERP RS

2.6

Varity_R

0.13

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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