15-91252418-T-A

Variant names:

• chr15-91252418-T-A
• NM_001323032.3:c.682T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001323032.3(SV2B):​c.682T>A​(p.Ser228Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,424 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SV2B NM_001323032.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

Genes affected

SV2B (HGNC:16874): (synaptic vesicle glycoprotein 2B) This gene encodes a member of the synaptic vesicle proteins 2 (SV2) family and major facilitator superfamily of proteins. This protein and other members of the family are localized to synaptic vesicles and may function in the regulation of vesicle trafficking and exocytosis. Studies in mice suggest that the encoded protein may act as a protein receptor for botulinum neurotoxin E in neurons, and that this protein may be important for the integrity of the glomerular filtration barrier. This gene shows reduced expression in areas of synaptic loss in the hippocampus of human temporal lobe epilepsy patients. [provided by RefSeq, Sep 2016]

ENSG00000301795 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323032.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2B	NM_001323032.3	MANE Select	c.682T>A	p.Ser228Thr	missense	Exon 4 of 13	NP_001309961.1	Q7L1I2-1
	SV2B	NM_001323031.2		c.682T>A	p.Ser228Thr	missense	Exon 4 of 13	NP_001309960.1	Q7L1I2-1
	SV2B	NM_001323037.3		c.682T>A	p.Ser228Thr	missense	Exon 5 of 14	NP_001309966.1	Q7L1I2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SV2B	ENST00000394232.6	TSL:5 MANE Select	c.682T>A	p.Ser228Thr	missense	Exon 4 of 13	ENSP00000377779.1	Q7L1I2-1
	SV2B	ENST00000330276.4	TSL:1	c.682T>A	p.Ser228Thr	missense	Exon 3 of 12	ENSP00000332818.4	Q7L1I2-1
	SV2B	ENST00000557410.5	TSL:1	n.682T>A		non_coding_transcript_exon	Exon 5 of 15	ENSP00000450992.1	Q7L1I2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461424 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726996

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111790

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.22
Sift	Uncertain	0.014	D
Sift4G	Benign	0.18	T
Polyphen		0.87	P
Vest4		0.56
MutPred		0.52		Loss of disorder (P = 0.0573)
MVP		0.51
MPC		0.48
ClinPred		0.87	D
GERP RS		5.4
Varity_R		0.22
gMVP		0.56

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

hg19: chr15-91795648;