chr5-76326989-C-A

Variant names:

• chr5-76326989-C-A
• rs3733860
• NM_014979.4:c.*1442C>A

Variant summary

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

The NM_014979.4(SV2C):​c.*1442C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,084 control chromosomes in the GnomAD database, including 1,765 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 0.12 (1765 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SV2C NM_014979.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 11 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]

ENSG00000250348 (HGNC:58251):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2C	NM_014979.4	c.*1442C>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000502798.7	NP_055794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SV2C	ENST00000502798.7	c.*1442C>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_014979.4	ENSP00000423541.2
SV2C	ENST00000322285.7	c.2000+25444C>A		intron_variant	Intron 12 of 12	2		ENSP00000316983.7
ENSG00000250348	ENST00000502589.2	n.531+9332G>T		intron_variant	Intron 1 of 3	5
ENSG00000250348	ENST00000784363.1	n.508+9332G>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18963 AN: 151964 Hom.: 1764 Cov.: 32

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.128

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.125 AC: 18966 AN: 152084 Hom.: 1765 Cov.: 32 AF XY: 0.125 AC XY: 9315 AN XY: 74330

African (AFR) AF: 0.0327 AC: 1356 AN: 41484

American (AMR) AF: 0.221 AC: 3383 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3468

East Asian (EAS) AF: 0.419 AC: 2153 AN: 5142

South Asian (SAS) AF: 0.125 AC: 601 AN: 4812

European-Finnish (FIN) AF: 0.126 AC: 1334 AN: 10574

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9425 AN: 67998

Other (OTH) AF: 0.127 AC: 269 AN: 2114

Alfa AF: 0.129 Hom.: 2870

Bravo AF: 0.130

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		0.036
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3733860; hg19: chr5-75622814; COSMIC: COSV59216979;