20-58670051-C-T

Variant names:

• chr20-58670051-C-T
• rs6100158
• NM_001001433.3:c.557-461C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001433.3(STX16):​c.557-461C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,110 control chromosomes in the GnomAD database, including 19,650 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 0.50 (19650 hom., cov: 33)
• Consequence: STX16 NM_001001433.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• 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.557-461C>T		intron	N/A	NP_001001433.1	O14662-1
	STX16	NM_001134772.3		c.545-461C>T		intron	N/A	NP_001128244.1	O14662-5
	STX16	NM_001134773.3		c.506-461C>T		intron	N/A	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.557-461C>T		intron	N/A	ENSP00000360183.4	O14662-1
	STX16	ENST00000358029.8	TSL:1	c.545-461C>T		intron	N/A	ENSP00000350723.4	O14662-5
	STX16	ENST00000371132.8	TSL:1	c.494-461C>T		intron	N/A	ENSP00000360173.4	O14662-2

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76740 AN: 151992 Hom.: 19629 Cov.: 33

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.505 AC: 76788 AN: 152110 Hom.: 19650 Cov.: 33 AF XY: 0.502 AC XY: 37333 AN XY: 74342

African (AFR) AF: 0.480 AC: 19912 AN: 41490

American (AMR) AF: 0.475 AC: 7260 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1960 AN: 3466

East Asian (EAS) AF: 0.432 AC: 2234 AN: 5176

South Asian (SAS) AF: 0.487 AC: 2343 AN: 4814

European-Finnish (FIN) AF: 0.495 AC: 5238 AN: 10578

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

European-Non Finnish (NFE) AF: 0.531 AC: 36100 AN: 67982

Other (OTH) AF: 0.503 AC: 1063 AN: 2112

Alfa AF: 0.520 Hom.: 2606

Bravo AF: 0.501

Asia WGS AF: 0.496 AC: 1725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.1
DANN	Benign	0.69
PhyloP100		0.051
Mutation Taster		=100/0	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: rs6100158; hg19: chr20-57245107;