rs31244

chr5-76298918-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014979.4(SV2C):c.1627G>A(p.Asp543Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 1,613,424 control chromosomes in the GnomAD database, including 6,155 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.10 (869 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5286 hom.)
• Consequence: SV2C NM_014979.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.22

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015901029).
• BP6: Variant 5-76298918-G-A is Benign according to our data. Variant chr5-76298918-G-A is described in ClinVar as [Benign]. Clinvar id is 3060811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SV2C	NM_014979.4	c.1627G>A	p.Asp543Asn	missense_variant	10/13	ENST00000502798.7
LOC105379042	XR_001742750.2	n.447-733C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SV2C	ENST00000502798.7	c.1627G>A	p.Asp543Asn	missense_variant	10/13	1	NM_014979.4	P1
	ENST00000502589.1	n.280-12115C>T		intron_variant, non_coding_transcript_variant		5
SV2C	ENST00000322285.7	c.1627G>A	p.Asp543Asn	missense_variant	10/13	2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15705 AN: 152090 Hom.: 866 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0951

GnomAD3 exomes AF: 0.0945 AC: 23529 AN: 248978 Hom.: 1355 AF XY: 0.0886 AC XY: 11968 AN XY: 135092

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.0928

Gnomad SAS exome AF: 0.0326

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0788

Gnomad OTH exome AF: 0.0873

GnomAD4 exome AF: 0.0813 AC: 118770 AN: 1461216 Hom.: 5286 Cov.: 31 AF XY: 0.0793 AC XY: 57652 AN XY: 726938

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.0954

Gnomad4 SAS exome AF: 0.0332

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0776

Gnomad4 OTH exome AF: 0.0804

GnomAD4 genome AF: 0.103 AC: 15718 AN: 152208 Hom.: 869 Cov.: 32 AF XY: 0.106 AC XY: 7896 AN XY: 74408

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0908

Gnomad4 SAS AF: 0.0309

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.0937

Alfa AF: 0.0839 Hom.: 1288

Bravo AF: 0.107

TwinsUK AF: 0.0844 AC: 313

ALSPAC AF: 0.0869 AC: 335

ESP6500AA AF: 0.139 AC: 528

ESP6500EA AF: 0.0737 AC: 606

ExAC AF: 0.0908 AC: 10970

Asia WGS AF: 0.0700 AC: 243 AN: 3478

EpiCase AF: 0.0747

EpiControl AF: 0.0745

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SV2C-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 01, 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	0.062
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.017	T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.76	T;T
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;.
MutationTaster	Benign	0.91	P;P
PrimateAI	Benign	0.30	T
PROVEAN	Benign	1.3	N;N
REVEL	Benign	0.071
Sift	Benign	0.27	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.0	B;.
Vest4		0.054
MPC		0.15
ClinPred		0.013	T
GERP RS		4.7
Varity_R		0.32
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs31244; hg19: chr5-75594743;