chr20-58652153-G-A

Position:

• chr20-58652153-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001001433.3(STX16):​c.132+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,612,964 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (31 hom.)
• Consequence: STX16 NM_001001433.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.22

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 20-58652153-G-A is Benign according to our data. Variant chr20-58652153-G-A is described in ClinVar as [Benign]. Clinvar id is 339044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-58652153-G-A is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 327 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX16	NM_001001433.3	c.132+15G>A		intron_variant		ENST00000371141.8
STX16-NPEPL1	NR_037945.1	n.886+15G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX16	ENST00000371141.8	c.132+15G>A		intron_variant		2	NM_001001433.3	P3

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 328 AN: 152188 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00381 AC: 944 AN: 247938 Hom.: 7 AF XY: 0.00474 AC XY: 636 AN XY: 134306

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.0200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0126

Gnomad FIN exome AF: 0.000337

Gnomad NFE exome AF: 0.00220

Gnomad OTH exome AF: 0.00622

GnomAD4 exome AF: 0.00234 AC: 3419 AN: 1460658 Hom.: 31 Cov.: 31 AF XY: 0.00278 AC XY: 2018 AN XY: 726682

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00199

Gnomad4 ASJ exome AF: 0.0199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0124

Gnomad4 FIN exome AF: 0.000343

Gnomad4 NFE exome AF: 0.00119

Gnomad4 OTH exome AF: 0.00480

GnomAD4 genome AF: 0.00215 AC: 327 AN: 152306 Hom.: 2 Cov.: 32 AF XY: 0.00235 AC XY: 175 AN XY: 74478

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00324 Hom.: 1

Bravo AF: 0.00196

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Pseudohypoparathyroidism type 1B Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs139859128; hg19: chr20-57227209;