16-19183806-C-A

Variant names:

• chr16-19183806-C-A
• rs150476528
• NM_016524.4:c.610C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016524.4(SYT17):​c.610C>A​(p.Arg204Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,226 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R204H) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SYT17 NM_016524.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 4 publications found

Genes affected

SYT17 (HGNC:24119): (synaptotagmin 17) Predicted to enable several functions, including calcium ion binding activity; phospholipid binding activity; and syntaxin binding activity. Involved in positive regulation of dendrite extension. Predicted to be located in trans-Golgi network. Predicted to be active in exocytic vesicle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286790 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016524.4. 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
	SYT17	NM_016524.4	MANE Select	c.610C>A	p.Arg204Ser	missense	Exon 5 of 8	NP_057608.2
	SYT17	NM_001308157.2		c.598C>A	p.Arg200Ser	missense	Exon 5 of 8	NP_001295086.1	H3BN78
	SYT17	NM_001330509.2		c.427C>A	p.Arg143Ser	missense	Exon 5 of 8	NP_001317438.1	H3BRH9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT17	ENST00000355377.7	TSL:1 MANE Select	c.610C>A	p.Arg204Ser	missense	Exon 5 of 8	ENSP00000347538.2	Q9BSW7
	SYT17	ENST00000562034.5	TSL:1	c.427C>A	p.Arg143Ser	missense	Exon 3 of 6	ENSP00000456252.1	H3BRH9
	SYT17	ENST00000971661.1		c.610C>A	p.Arg204Ser	missense	Exon 5 of 8	ENSP00000641720.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.029	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.34
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.67	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.018	D
Sift4G	Benign	0.29	T
Polyphen		0.0050	B
Vest4		0.76
MutPred		0.54		Loss of sheet (P = 0.1501)
MVP		0.27
MPC		0.54
ClinPred		0.77	D
GERP RS		-9.8
Varity_R		0.14
gMVP		0.70

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: rs150476528; hg19: chr16-19195128;