9-99961410-C-T

Variant names:

• chr9-99961410-C-T
• rs10760706
• NM_017919.3:c.582+1255C>T

Variant summary

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

The NM_017919.3(STX17):​c.582+1255C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,014 control chromosomes in the GnomAD database, including 36,204 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 0.69 (36204 hom., cov: 31)
• Consequence: STX17 NM_017919.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 26 publications found

Genes affected

STX17 (HGNC:11432): (syntaxin 17) Enables SNAP receptor activity; SNARE binding activity; and protein phosphatase binding activity. Involved in several processes, including autophagosome membrane docking; endoplasmic reticulum to Golgi vesicle-mediated transport; and endoplasmic reticulum-Golgi intermediate compartment organization. Acts upstream of or within protein localization to phagophore assembly site. Located in several cellular components, including autophagosome membrane; endoplasmic reticulum-Golgi intermediate compartment; and mitochondria-associated endoplasmic reticulum membrane. Part of SNARE complex. Colocalizes with HOPS complex. [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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX17	NM_017919.3	c.582+1255C>T		intron_variant	Intron 6 of 7	ENST00000259400.11	NP_060389.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX17	ENST00000259400.11	c.582+1255C>T		intron_variant	Intron 6 of 7	1	NM_017919.3	ENSP00000259400.6

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104430 AN: 151896 Hom.: 36175 Cov.: 31

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.652

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.688 AC: 104510 AN: 152014 Hom.: 36204 Cov.: 31 AF XY: 0.688 AC XY: 51136 AN XY: 74310

African (AFR) AF: 0.716 AC: 29695 AN: 41448

American (AMR) AF: 0.638 AC: 9747 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2063 AN: 3472

East Asian (EAS) AF: 0.713 AC: 3684 AN: 5170

South Asian (SAS) AF: 0.524 AC: 2517 AN: 4808

European-Finnish (FIN) AF: 0.781 AC: 8251 AN: 10564

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.684 AC: 46455 AN: 67958

Other (OTH) AF: 0.655 AC: 1380 AN: 2108

Alfa AF: 0.677 Hom.: 111495

Bravo AF: 0.681

Asia WGS AF: 0.638 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.6
DANN	Benign	0.24
PhyloP100		0.13
Mutation Taster		=100/0	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: rs10760706; hg19: chr9-102723692;