NM_031912.5:c.670A>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031912.5. 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
	SYT15	NM_031912.5	MANE Select	c.670A>T	p.Thr224Ser	missense	Exon 5 of 8	NP_114118.2
	SYT15	NM_181519.3		c.670A>T	p.Thr224Ser	missense	Exon 5 of 9	NP_852660.1	Q9BQS2-2
	SYT15-AS1	NR_155739.1		n.313-612T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT15	ENST00000374321.9	TSL:2 MANE Select	c.670A>T	p.Thr224Ser	missense	Exon 5 of 8	ENSP00000363441.4	Q9BQS2-1
	SYT15	ENST00000503753.5	TSL:1	c.670A>T	p.Thr224Ser	missense	Exon 5 of 9	ENSP00000427607.1	Q9BQS2-2
	SYT15	ENST00000374323.8	TSL:2	c.829A>T	p.Thr277Ser	missense	Exon 4 of 7	ENSP00000363443.3

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 9

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	0.073
BayesDel_noAF	Benign	-0.37
CADD	Benign	2.9
DANN	Benign	0.79
DEOGEN2	Benign	0.032	T
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.063	T
PhyloP100		0.32
PROVEAN	Benign	-1.2	N
Sift	Benign	0.42	T
Sift4G	Benign	0.61	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

Other links and lift over

hg19: chr10-46965867;