10-46582147-C-T

Variant names:

• chr10-46582147-C-T
• rs201185868
• NM_031912.5:c.607C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_031912.5(SYT15):​c.607C>T​(p.Arg203Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 152,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000093 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYT15 NM_031912.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.217

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=0.15338674).
• BP6: Variant 10-46582147-C-T is Benign according to our data. Variant chr10-46582147-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2566519.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT15	NM_031912.5	c.607C>T	p.Arg203Cys	missense_variant	Exon 4 of 8	ENST00000374321.9	NP_114118.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYT15	ENST00000374321.9	c.607C>T	p.Arg203Cys	missense_variant	Exon 4 of 8	2	NM_031912.5	ENSP00000363441.4

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152024 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000261 AC: 65 AN: 249216 Hom.: 0 AF XY: 0.000325 AC XY: 44 AN XY: 135200

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000278

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000331

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000926 AC: 135 AN: 1457148 Hom.: 0 Cov.: 32 AF XY: 0.000104 AC XY: 75 AN XY: 724600

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.000515

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.0000568

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152142 Hom.: 0 Cov.: 23 AF XY: 0.000161 AC XY: 12 AN XY: 74388

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 04, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T;.;T;.
LIST_S2	Benign	0.86	.;D;D;.
MetaRNN	Benign	0.15	T;T;T;T
PROVEAN	Pathogenic	-5.6	D;D;D;D
Sift	Uncertain	0.025	D;T;T;T
Sift4G	Benign	0.072	T;T;T;T
Vest4		0.29
gMVP		0.97

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

LitVar

Other links and lift over

dbSNP: rs201185868; hg19: chr10-46967470; COSMIC: COSV65432047; COSMIC: COSV65432047;