NM_001001433.3:c.540G>A

Variant names:

• chr20-58669437-G-A
• rs2296524
• NM_001001433.3:c.540G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001001433.3(STX16):​c.540G>A​(p.Gln180Gln) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.64
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001433.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX16	NM_001001433.3	MANE Select	c.540G>A	p.Gln180Gln	synonymous	Exon 5 of 9	NP_001001433.1	O14662-1
	STX16	NM_001134772.3		c.528G>A	p.Gln176Gln	synonymous	Exon 4 of 8	NP_001128244.1	O14662-5
	STX16	NM_001134773.3		c.489G>A	p.Gln163Gln	synonymous	Exon 5 of 9	NP_001128245.1	O14662-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX16	ENST00000371141.8	TSL:2 MANE Select	c.540G>A	p.Gln180Gln	synonymous	Exon 5 of 9	ENSP00000360183.4	O14662-1
	STX16	ENST00000358029.8	TSL:1	c.528G>A	p.Gln176Gln	synonymous	Exon 4 of 8	ENSP00000350723.4	O14662-5
	STX16	ENST00000371132.8	TSL:1	c.477G>A	p.Gln159Gln	synonymous	Exon 4 of 8	ENSP00000360173.4	O14662-2

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76738 AN: 152018 Hom.: 19636 Cov.: 33

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

GnomAD2 exomes AF: 0.492 AC: 119120 AN: 241908 AF XY: 0.496

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 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.: 59 AF XY: 0.519 AC XY: 376261 AN XY: 724978

African (AFR) AF: 0.479 AC: 15951 AN: 33292

American (AMR) AF: 0.431 AC: 18827 AN: 43706

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 14286 AN: 25892

East Asian (EAS) AF: 0.486 AC: 19255 AN: 39602

South Asian (SAS) AF: 0.493 AC: 42221 AN: 85716

European-Finnish (FIN) AF: 0.486 AC: 25568 AN: 52604

Middle Eastern (MID) AF: 0.544 AC: 3125 AN: 5742

European-Non Finnish (NFE) AF: 0.528 AC: 586112 AN: 1110508

Other (OTH) AF: 0.509 AC: 30647 AN: 60226

GnomAD4 genome AF: 0.505 AC: 76785 AN: 152136 Hom.: 19657 Cov.: 33 AF XY: 0.502 AC XY: 37338 AN XY: 74378

African (AFR) AF: 0.481 AC: 19949 AN: 41478

American (AMR) AF: 0.475 AC: 7266 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1952 AN: 3472

East Asian (EAS) AF: 0.432 AC: 2231 AN: 5168

South Asian (SAS) AF: 0.486 AC: 2345 AN: 4830

European-Finnish (FIN) AF: 0.494 AC: 5230 AN: 10582

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36103 AN: 67984

Other (OTH) AF: 0.506 AC: 1069 AN: 2114

Alfa AF: 0.513 Hom.: 27855

Bravo AF: 0.501

Asia WGS AF: 0.495 AC: 1721 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Pseudohypoparathyroidism type 1B (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.4
DANN	Benign	0.91
PhyloP100		4.6
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2296524; hg19: chr20-57244493; COSMIC: COSV56604484; COSMIC: COSV56604484;