16-19183806-C-T

Variant names:

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

Variant summary

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

The NM_016524.4(SYT17):​c.610C>T​(p.Arg204Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000457 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). 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 0.00036 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (0 hom.)
• Consequence: SYT17 NM_016524.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

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>T	p.Arg204Cys	missense	Exon 5 of 8	NP_057608.2
	SYT17	NM_001308157.2		c.598C>T	p.Arg200Cys	missense	Exon 5 of 8	NP_001295086.1	H3BN78
	SYT17	NM_001330509.2		c.427C>T	p.Arg143Cys	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>T	p.Arg204Cys	missense	Exon 5 of 8	ENSP00000347538.2	Q9BSW7
	SYT17	ENST00000562034.5	TSL:1	c.427C>T	p.Arg143Cys	missense	Exon 3 of 6	ENSP00000456252.1	H3BRH9
	SYT17	ENST00000971661.1		c.610C>T	p.Arg204Cys	missense	Exon 5 of 8	ENSP00000641720.1

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 55 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000676

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000322 AC: 81 AN: 251314 AF XY: 0.000339

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000660

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000467 AC: 682 AN: 1461846 Hom.: 0 Cov.: 31 AF XY: 0.000459 AC XY: 334 AN XY: 727218

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.0000937 AC: 5 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000593 AC: 659 AN: 1112012

Other (OTH) AF: 0.000199 AC: 12 AN: 60394

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74378

African (AFR) AF: 0.000169 AC: 7 AN: 41468

American (AMR) AF: 0.00 AC: 0 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: 0.000676 AC: 46 AN: 68038

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.000521 Hom.: 0

Bravo AF: 0.000287

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000338 AC: 41

EpiCase AF: 0.000327

EpiControl AF: 0.000593

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	Uncertain	0.50
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.077	N
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	-0.064	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.34
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.071	T
Polyphen		0.99	D
Vest4		0.77
MVP		0.65
MPC		1.1
ClinPred		0.68	D
GERP RS		-9.8
Varity_R		0.34
gMVP		0.72
Mutation Taster		=45/55	disease causing

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; COSMIC: COSV62545686; COSMIC: COSV62545686;