chr5-76132264-G-T

Variant names:

• chr5-76132264-G-T
• NM_014979.4:c.514G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014979.4(SV2C):​c.514G>T​(p.Val172Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SV2C NM_014979.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SV2C	NM_014979.4	c.514G>T	p.Val172Phe	missense_variant	Exon 2 of 13	ENST00000502798.7	NP_055794.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SV2C	ENST00000502798.7	c.514G>T	p.Val172Phe	missense_variant	Exon 2 of 13	1	NM_014979.4	ENSP00000423541.2
SV2C	ENST00000322285.7	c.514G>T	p.Val172Phe	missense_variant	Exon 2 of 13	2		ENSP00000316983.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461826 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727204

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;.
Vest4		0.93
MutPred		0.41		Gain of helix (P = 0.2059);Gain of helix (P = 0.2059);
MVP		0.85
MPC		0.76
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.78
gMVP		0.94

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-75428089;