10-46585694-A-C

Variant names:

• chr10-46585694-A-C
• rs1844823119
• NM_031912.5:c.1040A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_031912.5(SYT15):​c.1040A>C​(p.Glu347Ala) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 8)
  • Failed GnomAD Quality Control
• Consequence: SYT15 NM_031912.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.65
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.775

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.1040A>C	p.Glu347Ala	missense	Exon 7 of 8	NP_114118.2
	SYT15	NM_181519.3		c.1040A>C	p.Glu347Ala	missense	Exon 7 of 9	NP_852660.1	Q9BQS2-2
	SYT15-AS1	NR_155739.1		n.313-2556T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT15	ENST00000374321.9	TSL:2 MANE Select	c.1040A>C	p.Glu347Ala	missense	Exon 7 of 8	ENSP00000363441.4	Q9BQS2-1
	SYT15	ENST00000503753.5	TSL:1	c.1040A>C	p.Glu347Ala	missense	Exon 7 of 9	ENSP00000427607.1	Q9BQS2-2
	SYT15	ENST00000374323.8	TSL:2	c.1199A>C	p.Glu400Ala	missense	Exon 6 of 7	ENSP00000363443.3

Frequencies

GnomAD3 genomes AF: 0.0000165 AC: 1 AN: 60704 Hom.: 0 Cov.: 8

Gnomad AFR AF: 0.0000866

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 2

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000165 AC: 1 AN: 60704 Hom.: 0 Cov.: 8 AF XY: 0.0000350 AC XY: 1 AN XY: 28542

African (AFR) AF: 0.0000866 AC: 1 AN: 11544

American (AMR) AF: 0.00 AC: 0 AN: 5486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1838

East Asian (EAS) AF: 0.00 AC: 0 AN: 1852

South Asian (SAS) AF: 0.00 AC: 0 AN: 1046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 33544

Other (OTH) AF: 0.00 AC: 0 AN: 640

Alfa AF: 0.00 Hom.: 0

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	Pathogenic	0.78
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Pathogenic	0.78	D
PhyloP100		6.6
PROVEAN	Pathogenic	-5.2	D
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Vest4		0.83
gMVP		0.99

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

dbSNP: rs1844823119; hg19: chr10-46963923;