10-46580995-C-T

Variant names:

• chr10-46580995-C-T
• rs577411839
• NM_031912.5:c.314C>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.314C>T​(p.Pro105Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (4 hom., cov: 22)
  • Exomes 𝑓: 0.000044 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYT15 NM_031912.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.384
• Publications: 1 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=0.033035904).

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.314C>T	p.Pro105Leu	missense	Exon 3 of 8	NP_114118.2
	SYT15	NM_181519.3		c.314C>T	p.Pro105Leu	missense	Exon 3 of 9	NP_852660.1	Q9BQS2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT15	ENST00000374321.9	TSL:2 MANE Select	c.314C>T	p.Pro105Leu	missense	Exon 3 of 8	ENSP00000363441.4	Q9BQS2-1
	SYT15	ENST00000503753.5	TSL:1	c.314C>T	p.Pro105Leu	missense	Exon 3 of 9	ENSP00000427607.1	Q9BQS2-2
	SYT15	ENST00000374323.8	TSL:2	c.473C>T	p.Pro158Leu	missense	Exon 2 of 7	ENSP00000363443.3

Frequencies

GnomAD3 genomes AF: 0.000134 AC: 18 AN: 134432 Hom.: 4 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000879

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: 0.0000952

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000524 AC: 13 AN: 248190 AF XY: 0.0000371

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000356

Gnomad OTH exome AF: 0.000166

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000439 AC: 45 AN: 1025138 Hom.: 4 Cov.: 14 AF XY: 0.0000296 AC XY: 15 AN XY: 506910

African (AFR) AF: 0.0000491 AC: 1 AN: 20376

American (AMR) AF: 0.000203 AC: 5 AN: 24656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17504

East Asian (EAS) AF: 0.0000589 AC: 2 AN: 33972

South Asian (SAS) AF: 0.0000168 AC: 1 AN: 59480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31906

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3416

European-Non Finnish (NFE) AF: 0.0000380 AC: 30 AN: 789468

Other (OTH) AF: 0.000135 AC: 6 AN: 44360

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000134 AC: 18 AN: 134530 Hom.: 4 Cov.: 22 AF XY: 0.000107 AC XY: 7 AN XY: 65240

African (AFR) AF: 0.00 AC: 0 AN: 33582

American (AMR) AF: 0.000878 AC: 12 AN: 13664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3252

East Asian (EAS) AF: 0.00 AC: 0 AN: 4636

South Asian (SAS) AF: 0.00 AC: 0 AN: 4080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.0000953 AC: 6 AN: 62990

Other (OTH) AF: 0.00 AC: 0 AN: 1786

Alfa AF: 0.0000712 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	Benign	0.063
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.1
DANN	Benign	0.54
DEOGEN2	Benign	0.0059	T
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.033	T
PhyloP100		-0.38
PROVEAN	Benign	-0.96	N
Sift	Benign	0.14	T
Sift4G	Benign	1.0	T
Vest4		0.16
gMVP		0.80

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: rs577411839; hg19: chr10-46968622; COSMIC: COSV65430650; COSMIC: COSV65430650;