10-46582124-G-A

Variant names:

• chr10-46582124-G-A
• rs201664076
• NM_031912.5:c.584G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031912.5(SYT15):​c.584G>A​(p.Arg195His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 151,664 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 22)
  • Exomes 𝑓: 0.000087 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYT15 NM_031912.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2483032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYT15	NM_031912.5	c.584G>A	p.Arg195His	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.584G>A	p.Arg195His	missense_variant	Exon 4 of 8	2	NM_031912.5	ENSP00000363441.4

Frequencies

GnomAD3 genomes AF: 0.0000924 AC: 14 AN: 151542 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000124 AC: 31 AN: 249210 Hom.: 0 AF XY: 0.000118 AC XY: 16 AN XY: 135204

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.000446

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000973

Gnomad OTH exome AF: 0.000165

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000870 AC: 126 AN: 1447958 Hom.: 0 Cov.: 31 AF XY: 0.0000917 AC XY: 66 AN XY: 719432

Gnomad4 AFR exome AF: 0.000122

Gnomad4 AMR exome AF: 0.000116

Gnomad4 ASJ exome AF: 0.000120

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.0000359

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000751

Gnomad4 OTH exome AF: 0.000167

GnomAD4 genome AF: 0.0000923 AC: 14 AN: 151664 Hom.: 0 Cov.: 22 AF XY: 0.000135 AC XY: 10 AN XY: 74108

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.584G>A (p.R195H) alteration is located in exon 4 (coding exon 4) of the SYT15 gene. This alteration results from a G to A substitution at nucleotide position 584, causing the arginine (R) at amino acid position 195 to be replaced by a histidine (H). 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	0.091
BayesDel_noAF	Benign	-0.15
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.;T;.
LIST_S2	Benign	0.86	.;D;D;.
MetaRNN	Benign	0.25	T;T;T;T
PROVEAN	Uncertain	-3.6	D;D;D;D
Sift	Benign	0.088	T;D;D;D
Sift4G	Uncertain	0.010	D;T;D;D
Vest4		0.28
gMVP		0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201664076; hg19: chr10-46967493; COSMIC: COSV100970712; COSMIC: COSV100970712;