rs117681965

Variant names:

• chr11-85711173-C-A
• rs117681965
• NM_206927.4:c.5685G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-85711173-C-A
• chr11-85711173-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_206927.4(SYTL2):​c.5685G>T​(p.Lys1895Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYTL2 NM_206927.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 5 publications found

Genes affected

SYTL2 (HGNC:15585): (synaptotagmin like 2) The protein encoded by this gene is a synaptotagmin-like protein (SLP) that belongs to a C2 domain-containing protein family. The SLP homology domain (SHD) of this protein has been shown to specifically bind the GTP-bound form of Ras-related protein Rab-27A (RAB27A). This protein plays a role in RAB27A-dependent vesicle trafficking and controls melanosome distribution in the cell periphery. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Jun 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34895182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYTL2	NM_206927.4	c.5685G>T	p.Lys1895Asn	missense_variant	Exon 13 of 20	ENST00000359152.10	NP_996810.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYTL2	ENST00000359152.10	c.5685G>T	p.Lys1895Asn	missense_variant	Exon 13 of 20	1	NM_206927.4	ENSP00000352065.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;.;.;.;.;.;T;.;.;.;T;T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;.;.;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.35	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	.;.;.;.;.;.;M;.;.;.;.;.;.
PhyloP100		2.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.8	.;.;D;D;D;D;D;D;.;D;D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0050	.;.;D;D;D;D;D;D;.;D;D;D;D
Sift4G	Uncertain	0.018	D;D;D;T;T;T;D;D;D;.;.;.;.
Polyphen		0.99	D;.;D;.;.;P;D;D;.;.;.;.;.
Vest4		0.28
MutPred		0.25		.;.;.;.;.;.;Loss of ubiquitination at K590 (P = 0.0067);.;.;.;.;.;.;
MVP		0.57
MPC		0.094
ClinPred		0.98	D
GERP RS		6.1
Varity_R		0.34
gMVP		0.36
Mutation Taster		=99/1	polymorphism

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: rs117681965; hg19: chr11-85422216;