Variant 20-58651657-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001001433.3(STX16):c.-350C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 251,442 control chromosomes in the GnomAD database, including 531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 276 hom., cov: 32)

Exomes 𝑓: 0.065 ( 255 hom. )

Consequence

STX16
NM_001001433.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.722

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 20-58651657-C-A is Benign according to our data. Variant chr20-58651657-C-A is described in ClinVar as [Benign]. Clinvar id is 339040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0695 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.-350C>A		5_prime_UTR_variant	1/9	ENST00000371141.8
STX16-NPEPL1	NR_037945.1 linkuse as main transcript	n.405C>A		non_coding_transcript_exon_variant	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX16	ENST00000371141.8 linkuse as main transcript	c.-350C>A		5_prime_UTR_variant	1/9	2	NM_001001433.3	P3	O14662-1

Frequencies

GnomAD3 genomes

AF:

0.0513

AC:

7802

AN:

152184

Hom.:

275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0594

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0662

Gnomad FIN

AF:

0.0577

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0712

Gnomad OTH

AF:

0.0622

GnomAD4 exome

AF:

0.0654

AC:

6481

AN:

99140

Hom.:

255

Cov.:

AF XY:

0.0645

AC XY:

3428

AN XY:

53174

show subpopulations

Gnomad4 AFR exome

AF:

0.0165

Gnomad4 AMR exome

AF:

0.0599

Gnomad4 ASJ exome

AF:

0.0663

Gnomad4 EAS exome

AF:

0.000438

Gnomad4 SAS exome

AF:

0.0651

Gnomad4 FIN exome

AF:

0.0663

Gnomad4 NFE exome

AF:

0.0736

Gnomad4 OTH exome

AF:

0.0645

GnomAD4 genome

AF:

0.0512

AC:

7802

AN:

152302

Hom.:

276

Cov.:

AF XY:

0.0517

AC XY:

3848

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0161

Gnomad4 AMR

AF:

0.0593

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0661

Gnomad4 FIN

AF:

0.0577

Gnomad4 NFE

AF:

0.0712

Gnomad4 OTH

AF:

0.0639

Alfa

AF:

0.0483

Hom.:

Bravo

AF:

0.0500

Asia WGS

AF:

0.0350

AC:

120

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pseudohypoparathyroidism type 1B

Benign:1

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:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.2

DANN

Benign

0.87

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