rs2296524

Positions:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.64

Variant links:

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 links:

STX16-NPEPL1 (HGNC:):

STX16-NPEPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.540G>A	p.Gln180=	synonymous_variant	5/9	ENST00000371141.8
STX16-NPEPL1	NR_037945.1 linkuse as main transcript	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 linkuse as main transcript	c.540G>A	p.Gln180=	synonymous_variant	5/9	2	NM_001001433.3	P3	O14662-1

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76738

AN:

152018

Hom.:

19636

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.519

AC XY:

376261

AN XY:

724978

show subpopulations

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.:

AF XY:

0.502

AC XY:

37338

AN XY:

74378

show subpopulations

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Pseudohypoparathyroidism type 1B

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over