rs2296524

Variant names:

• chr20-58669437-G-A
• rs2296524
• NM_001001433.3:c.540G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001001433.3(STX16):​c.540G>A​(p.Gln180Gln) 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:5
• Conservation: PhyloP100: 4.64
• Publications: 26 publications found

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:41993): (STX16-NPEPL1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring syntaxin 16 (STX16) and aminopeptidase-like 1 (NPEPL1) genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
STX16	NM_001001433.3	c.540G>A	p.Gln180Gln	synonymous_variant	Exon 5 of 9	ENST00000371141.8	NP_001001433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX16	ENST00000371141.8	c.540G>A	p.Gln180Gln	synonymous_variant	Exon 5 of 9	2	NM_001001433.3	ENSP00000360183.4
STX16-NPEPL1	ENST00000530122.1	n.540G>A		non_coding_transcript_exon_variant	Exon 5 of 23	5		ENSP00000457522.1

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

GnomAD2 exomes AF: 0.492 AC: 119120 AN: 241908 AF XY: 0.496

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 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

African (AFR) AF: 0.479 AC: 15951 AN: 33292

American (AMR) AF: 0.431 AC: 18827 AN: 43706

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 14286 AN: 25892

East Asian (EAS) AF: 0.486 AC: 19255 AN: 39602

South Asian (SAS) AF: 0.493 AC: 42221 AN: 85716

European-Finnish (FIN) AF: 0.486 AC: 25568 AN: 52604

Middle Eastern (MID) AF: 0.544 AC: 3125 AN: 5742

European-Non Finnish (NFE) AF: 0.528 AC: 586112 AN: 1110508

Other (OTH) AF: 0.509 AC: 30647 AN: 60226

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

African (AFR) AF: 0.481 AC: 19949 AN: 41478

American (AMR) AF: 0.475 AC: 7266 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1952 AN: 3472

East Asian (EAS) AF: 0.432 AC: 2231 AN: 5168

South Asian (SAS) AF: 0.486 AC: 2345 AN: 4830

European-Finnish (FIN) AF: 0.494 AC: 5230 AN: 10582

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36103 AN: 67984

Other (OTH) AF: 0.506 AC: 1069 AN: 2114

Alfa AF: 0.513 Hom.: 27855

Bravo AF: 0.501

Asia WGS AF: 0.495 AC: 1721 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Pseudohypoparathyroidism type 1B Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.4
DANN	Benign	0.91
PhyloP100		4.6
Mutation Taster		=99/1	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: rs2296524; hg19: chr20-57244493; COSMIC: COSV56604484; COSMIC: COSV56604484;