rs229018

Variant names:

• chr16-19211391-T-G
• rs229018
• NM_016524.4:c.952-11654T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016524.4(SYT17):​c.952-11654T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 703,124 control chromosomes in the GnomAD database, including 22,324 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6273 hom., cov: 31)
  • Exomes 𝑓: 0.23 (16051 hom.)
• Consequence: SYT17 NM_016524.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 6 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT17	NM_016524.4	MANE Select	c.952-11654T>G		intron	N/A	NP_057608.2
	SYT17	NM_001308157.2		c.940-11654T>G		intron	N/A	NP_001295086.1
	SYT17	NM_001330509.2		c.769-11654T>G		intron	N/A	NP_001317438.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT17	ENST00000355377.7	TSL:1 MANE Select	c.952-11654T>G		intron	N/A	ENSP00000347538.2
	SYT17	ENST00000562034.5	TSL:1	c.769-11654T>G		intron	N/A	ENSP00000456252.1
	SYT17	ENST00000568433.1	TSL:3	c.-29T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000456915.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42009 AN: 151822 Hom.: 6264 Cov.: 31

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.249

GnomAD2 exomes AF: 0.227 AC: 31049 AN: 136930 AF XY: 0.223

Gnomad AFR exome AF: 0.377

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.305

Gnomad EAS exome AF: 0.112

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.258

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.232 AC: 128111 AN: 551184 Hom.: 16051 Cov.: 0 AF XY: 0.228 AC XY: 68062 AN XY: 298358

African (AFR) AF: 0.381 AC: 6006 AN: 15784

American (AMR) AF: 0.194 AC: 6735 AN: 34688

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 6117 AN: 20012

East Asian (EAS) AF: 0.0889 AC: 2854 AN: 32090

South Asian (SAS) AF: 0.171 AC: 10709 AN: 62732

European-Finnish (FIN) AF: 0.222 AC: 7687 AN: 34628

Middle Eastern (MID) AF: 0.213 AC: 866 AN: 4068

European-Non Finnish (NFE) AF: 0.252 AC: 79687 AN: 316610

Other (OTH) AF: 0.244 AC: 7450 AN: 30572

GnomAD4 genome AF: 0.277 AC: 42051 AN: 151940 Hom.: 6273 Cov.: 31 AF XY: 0.272 AC XY: 20241 AN XY: 74300

African (AFR) AF: 0.379 AC: 15704 AN: 41388

American (AMR) AF: 0.228 AC: 3473 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1029 AN: 3470

East Asian (EAS) AF: 0.113 AC: 583 AN: 5162

South Asian (SAS) AF: 0.163 AC: 783 AN: 4818

European-Finnish (FIN) AF: 0.228 AC: 2409 AN: 10570

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17139 AN: 67966

Other (OTH) AF: 0.247 AC: 519 AN: 2104

Alfa AF: 0.254 Hom.: 4911

Bravo AF: 0.283

Asia WGS AF: 0.145 AC: 503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.42
PhyloP100		-0.65
PromoterAI		-0.0012	Neutral
Mutation Taster		=296/4	polymorphism (auto)

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: rs229018; hg19: chr16-19222713;