Variant chr5-76295885-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000502798.7(SV2C):c.1445C>G(p.Thr482Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,612,150 control chromosomes in the GnomAD database, including 12,779 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.16 ( 2350 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10429 hom. )

Consequence

SV2C
ENST00000502798.7 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.356

Variant links:

Genes affected

SV2C (HGNC:30670): (synaptic vesicle glycoprotein 2C) Predicted to enable transmembrane transporter activity. Predicted to be involved in chemical synaptic transmission; neurotransmitter transport; and transmembrane transport. Predicted to be located in plasma membrane and synaptic vesicle. Predicted to be active in neuron projection and synaptic vesicle membrane. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

SV2C links:

SV2C (HGNC:):

SV2C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033721626).

BP6

Variant 5-76295885-C-G is Benign according to our data. Variant chr5-76295885-C-G is described in ClinVar as [Benign]. Clinvar id is 3059133.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SV2C	NM_014979.4 linkuse as main transcript	c.1445C>G	p.Thr482Ser	missense_variant	9/13	ENST00000502798.7	NP_055794.3	Q496J9B3KT41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SV2C	ENST00000502798.7 linkuse as main transcript	c.1445C>G	p.Thr482Ser	missense_variant	9/13	1	NM_014979.4	ENSP00000423541.2	Q496J9
SV2C	ENST00000322285.7 linkuse as main transcript	c.1445C>G	p.Thr482Ser	missense_variant	9/13	2		ENSP00000316983.7	B3KT41
SV2C	ENST00000506257.1 linkuse as main transcript	n.200C>G		non_coding_transcript_exon_variant	2/2	3
ENSG00000250348	ENST00000502589.1 linkuse as main transcript	n.280-9082G>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24383

AN:

152018

Hom.:

2338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.0979

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.141

AC:

34937

AN:

248140

Hom.:

2825

AF XY:

0.137

AC XY:

18385

AN XY:

134652

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.180

Gnomad SAS exome

AF:

0.140

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.112

AC:

163560

AN:

1460014

Hom.:

10429

Cov.:

AF XY:

0.112

AC XY:

81674

AN XY:

726280

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.189

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.201

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.0959

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.161

AC:

24421

AN:

152136

Hom.:

2350

Cov.:

AF XY:

0.164

AC XY:

12228

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.210

Gnomad4 EAS

AF:

0.180

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.0979

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.0972

Hom.:

279

Bravo

AF:

0.168

TwinsUK

AF:

0.102

AC:

380

ALSPAC

AF:

0.106

AC:

409

ESP6500AA

AF:

0.258

AC:

949

ESP6500EA

AF:

0.101

AC:

821

ExAC

AF:

0.140

AC:

16957

Asia WGS

AF:

0.191

AC:

662

AN:

3478

EpiCase

AF:

0.0995

EpiControl

AF:

0.0994

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SV2C-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.035

T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.038

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.97

N;N

REVEL

Benign

0.18

Sift

Benign

0.27

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.0

B;.

Vest4

0.014

MutPred

0.20

Gain of ubiquitination at K477 (P = 0.1204);Gain of ubiquitination at K477 (P = 0.1204);

MPC

0.13

ClinPred

0.0090

GERP RS

0.66

Varity_R

0.17

gMVP

0.61

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