rs2270927

chr5-76295885-C-Achr5-76295885-C-Gchr5-76295885-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 16/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10248932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SV2C	NM_014979.4	c.1445C>A	p.Thr482Asn	missense_variant	9/13	ENST00000502798.7
LOC105379042	XR_001742750.2	n.530-41G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SV2C	ENST00000502798.7	c.1445C>A	p.Thr482Asn	missense_variant	9/13	1	NM_014979.4	P1
	ENST00000502589.1	n.280-9082G>T		intron_variant, non_coding_transcript_variant		5
SV2C	ENST00000322285.7	c.1445C>A	p.Thr482Asn	missense_variant	9/13	2
SV2C	ENST00000506257.1	n.200C>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152056 Hom.: 0 Cov.: 32

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: 2 AN: 1460698 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726644

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152056 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74258

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	18
Dann	Benign	0.96
DEOGEN2	Benign	0.054	T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.11	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.14
Sift	Benign	0.14	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.0	B;.
Vest4		0.084
MutPred		0.42		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.61
MPC		0.17
ClinPred		0.23	T
GERP RS		0.66
Varity_R		0.19
gMVP		0.81

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

Other links and lift over

dbSNP: rs2270927; hg19: chr5-75591710;