20-58659426-A-G

Position:

• chr20-58659426-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001001433.3(STX16):​c.133-197A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 152,082 control chromosomes in the GnomAD database, including 533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.080 (533 hom., cov: 32)
• Consequence: STX16 NM_001001433.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.312

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]

STX16 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-58659426-A-G is Benign according to our data. Variant chr20-58659426-A-G is described in ClinVar as [Benign]. Clinvar id is 1283944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX16	NM_001001433.3	c.133-197A>G		intron_variant		ENST00000371141.8	NP_001001433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX16	ENST00000371141.8	c.133-197A>G		intron_variant		2	NM_001001433.3	ENSP00000360183.4
STX16-NPEPL1	ENST00000530122.1	n.133-197A>G		intron_variant		5		ENSP00000457522.1

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12110 AN: 151968 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.0964

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.0796 AC: 12112 AN: 152082 Hom.: 533 Cov.: 32 AF XY: 0.0795 AC XY: 5910 AN XY: 74360

Gnomad4 AFR AF: 0.0962

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.0701

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0705

Gnomad4 FIN AF: 0.0814

Gnomad4 NFE AF: 0.0789

Gnomad4 OTH AF: 0.0824

Alfa AF: 0.0299 Hom.: 14

Bravo AF: 0.0794

Asia WGS AF: 0.0360 AC: 126 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.69

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: rs16982214; hg19: chr20-57234482;