10-46585630-A-T

Position:

• chr10-46585630-A-T

Variant summary

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

The NM_031912.5(SYT15):​c.976A>T​(p.Asn326Tyr) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 7)
• Consequence: SYT15 NM_031912.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.89

Genes affected

SYT15 (HGNC:17167): (synaptotagmin 15) This gene encodes a member of the Synaptotagmin (Syt) family of membrane trafficking proteins. Members of this family contain a transmembrane region and a C-terminal-type tandem C2 domain. Unlike related family members, the encoded protein may be involved in membrane trafficking in non-neuronal tissues. Two trancript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SYT15-AS1 (HGNC:56167): (SYT15 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYT15	NM_031912.5	c.976A>T	p.Asn326Tyr	missense_variant	7/8	ENST00000374321.9	NP_114118.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYT15	ENST00000374321.9	c.976A>T	p.Asn326Tyr	missense_variant	7/8	2	NM_031912.5	ENSP00000363441.4

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.976A>T (p.N326Y) alteration is located in exon 7 (coding exon 7) of the SYT15 gene. This alteration results from a A to T substitution at nucleotide position 976, causing the asparagine (N) at amino acid position 326 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T;.;.
LIST_S2	Benign	0.82	.;T;.;T
MetaRNN	Uncertain	0.73	D;D;D;D
PROVEAN	Pathogenic	-4.8	D;D;D;D
Sift	Benign	0.13	T;D;T;D
Sift4G	Uncertain	0.010	D;D;D;D
Vest4		0.52
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-46963987;