Genetic Variant SV2C:p.Thr482Asn (chr5-76295885-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014979.4(SV2C):c.1445C>A(p.Thr482Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T482S) has been classified as Benign.

Frequency

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

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SV2C
NM_014979.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.356

Publications

25 publications found

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:

ENSG00000250348 (HGNC:58251):

ENSG00000250348 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10248932).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014979.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2C	NM_014979.4	MANE Select	c.1445C>A	p.Thr482Asn	missense	Exon 9 of 13	NP_055794.3
	SV2C	NM_001297716.2		c.1445C>A	p.Thr482Asn	missense	Exon 9 of 13	NP_001284645.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SV2C	ENST00000502798.7	TSL:1 MANE Select	c.1445C>A	p.Thr482Asn	missense	Exon 9 of 13	ENSP00000423541.2
SV2C	ENST00000322285.7	TSL:2	c.1445C>A	p.Thr482Asn	missense	Exon 9 of 13	ENSP00000316983.7
SV2C	ENST00000506257.1	TSL:3	n.200C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152056

Hom.:

Cov.:

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726644

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33420

American (AMR)

AF:

0.00

AC:

AN:

44496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26096

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.00

AC:

AN:

86108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111454

Other (OTH)

AF:

0.00

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152056

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41406

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.054

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.11

M_CAP

Benign

0.023

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.61

MutationAssessor

Benign

1.8

PhyloP100

0.36

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Benign

0.14

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.084

MutPred

0.42

Gain of sheet (P = 0.0477)

MVP

0.61

MPC

0.17

ClinPred

0.23

GERP RS

0.66

Varity_R

0.19

gMVP

0.81

Mutation Taster

=80/20

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over