rs2296524

Positions:

• chr20-58669437-G-A
• chr20-58669437-G-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001001433.3(STX16):​c.540G>A​(p.Gln180=) variant causes a synonymous change. The variant allele was found at a frequency of 0.517 in 1,609,424 control chromosomes in the GnomAD database, including 216,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19657 hom., cov: 33)
  • Exomes 𝑓: 0.52 (197134 hom.)
• Consequence: STX16 NM_001001433.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.64

Genes affected

STX16 (HGNC:11431): (syntaxin 16) This gene encodes a protein that is a member of the syntaxin or t-SNARE (target-SNAP receptor) family. These proteins are found on cell membranes and serve as the targets for V-SNARES (vesicle-SNAP receptors) permitting specific synaptic vesicle docking and fusion. A microdeletion in the region of chromosome 20 where this gene is located has been associated with pseudohypoparathyroidism type Ib. Multiple transcript variants have been found for this gene. Read-through transcription also exists between this gene and the neighboring downstream aminopeptidase-like 1 (NPEPL1) gene. [provided by RefSeq, Mar 2011]

STX16-NPEPL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 20-58669437-G-A is Benign according to our data. Variant chr20-58669437-G-A is described in ClinVar as [Benign]. Clinvar id is 339050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX16	NM_001001433.3	c.540G>A	p.Gln180=	synonymous_variant	5/9	ENST00000371141.8
STX16-NPEPL1	NR_037945.1	n.1294G>A		non_coding_transcript_exon_variant	5/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX16	ENST00000371141.8	c.540G>A	p.Gln180=	synonymous_variant	5/9	2	NM_001001433.3	P3

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76738 AN: 152018 Hom.: 19636 Cov.: 33

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.504

GnomAD3 exomes AF: 0.492 AC: 119120 AN: 241908 Hom.: 29530 AF XY: 0.496 AC XY: 65359 AN XY: 131730

Gnomad AFR exome AF: 0.480

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.543

Gnomad EAS exome AF: 0.432

Gnomad SAS exome AF: 0.492

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.521

Gnomad OTH exome AF: 0.490

GnomAD4 exome AF: 0.519 AC: 755992 AN: 1457288 Hom.: 197134 Cov.: 59 AF XY: 0.519 AC XY: 376261 AN XY: 724978

Gnomad4 AFR exome AF: 0.479

Gnomad4 AMR exome AF: 0.431

Gnomad4 ASJ exome AF: 0.552

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.528

Gnomad4 OTH exome AF: 0.509

GnomAD4 genome AF: 0.505 AC: 76785 AN: 152136 Hom.: 19657 Cov.: 33 AF XY: 0.502 AC XY: 37338 AN XY: 74378

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.506

Alfa AF: 0.513 Hom.: 19012

Bravo AF: 0.501

Asia WGS AF: 0.495 AC: 1721 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Pseudohypoparathyroidism type 1B Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.4
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs2296524; hg19: chr20-57244493; COSMIC: COSV56604484; COSMIC: COSV56604484;