5-76353455-C-T

Variant names:

• chr5-76353455-C-T
• rs73117804
• NM_001297716.2:c.*295C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297716.2(SV2C):​c.*295C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 158,762 control chromosomes in the GnomAD database, including 165 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.032 (165 hom., cov: 32)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: SV2C NM_001297716.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2C	NM_001297716.2	c.*295C>T		3_prime_UTR_variant	Exon 13 of 13		NP_001284645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SV2C	ENST00000322285.7	c.*295C>T		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000316983.7

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4809 AN: 152090 Hom.: 164 Cov.: 32

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.00359

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.0110 AC: 72 AN: 6554 Hom.: 0 Cov.: 0 AF XY: 0.00888 AC XY: 31 AN XY: 3492

African (AFR) AF: 0.117 AC: 7 AN: 60

American (AMR) AF: 0.00904 AC: 3 AN: 332

Ashkenazi Jewish (ASJ) AF: 0.00714 AC: 1 AN: 140

East Asian (EAS) AF: 0.00 AC: 0 AN: 74

South Asian (SAS) AF: 0.00516 AC: 6 AN: 1162

European-Finnish (FIN) AF: 0.00562 AC: 3 AN: 534

Middle Eastern (MID) AF: 0.0455 AC: 1 AN: 22

European-Non Finnish (NFE) AF: 0.0112 AC: 44 AN: 3946

Other (OTH) AF: 0.0246 AC: 7 AN: 284

GnomAD4 genome AF: 0.0317 AC: 4824 AN: 152208 Hom.: 165 Cov.: 32 AF XY: 0.0299 AC XY: 2227 AN XY: 74434

African (AFR) AF: 0.0851 AC: 3530 AN: 41492

American (AMR) AF: 0.0156 AC: 239 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4824

European-Finnish (FIN) AF: 0.00359 AC: 38 AN: 10594

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0121 AC: 826 AN: 68024

Other (OTH) AF: 0.0270 AC: 57 AN: 2114

Alfa AF: 0.0306 Hom.: 103

Bravo AF: 0.0351

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.34
DANN	Benign	0.47
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs73117804; hg19: chr5-75649280;