20-58668684-C-T

Position:

• chr20-58668684-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001433.3(STX16):​c.393+557C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 150,462 control chromosomes in the GnomAD database, including 17,948 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (17948 hom., cov: 27)
• Consequence: STX16 NM_001001433.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX16	NM_001001433.3	c.393+557C>T		intron_variant		ENST00000371141.8	NP_001001433.1
STX16-NPEPL1	NR_037945.1	n.1147+557C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX16	ENST00000371141.8	c.393+557C>T		intron_variant		2	NM_001001433.3	ENSP00000360183	P3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 72427 AN: 150346 Hom.: 17927 Cov.: 27

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.482 AC: 72480 AN: 150462 Hom.: 17948 Cov.: 27 AF XY: 0.479 AC XY: 35189 AN XY: 73424

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.483

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.486

Alfa AF: 0.388 Hom.: 1103

Bravo AF: 0.477

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.67
DANN	Benign	0.64

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: rs6100157; hg19: chr20-57243740; COSMIC: COSV56608601; COSMIC: COSV56608601;