10-46583750-A-T

Variant names:

• chr10-46583750-A-T
• NM_031912.5:c.670A>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031912.5(SYT15):​c.670A>T​(p.Thr224Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 9)
• Consequence: SYT15 NM_031912.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.321

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06278962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT15	NM_031912.5	c.670A>T	p.Thr224Ser	missense_variant	Exon 5 of 8	ENST00000374321.9	NP_114118.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT15	ENST00000374321.9	c.670A>T	p.Thr224Ser	missense_variant	Exon 5 of 8	2	NM_031912.5	ENSP00000363441.4

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 9

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.670A>T (p.T224S) alteration is located in exon 5 (coding exon 5) of the SYT15 gene. This alteration results from a A to T substitution at nucleotide position 670, causing the threonine (T) at amino acid position 224 to be replaced by a serine (S). 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	Benign	0.073
BayesDel_noAF	Benign	-0.37
CADD	Benign	2.9
DANN	Benign	0.79
DEOGEN2	Benign	0.032	T;.;T;.;.
LIST_S2	Benign	0.58	.;T;T;.;T
MetaRNN	Benign	0.063	T;T;T;T;T
PROVEAN	Benign	-1.2	N;N;N;N;N
Sift	Benign	0.42	T;T;T;T;T
Sift4G	Benign	0.61	T;T;T;T;T
Vest4		0.36
gMVP		0.65

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: chr10-46965867;