rs142560013

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001001433.3(STX16):c.106C>A(p.Pro36Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000883 in 1,614,172 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P36S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 1 hom. )

Consequence

STX16
NM_001001433.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.12

Publications

4 publications found

Variant links:

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 links:

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-NPEPL1 links:

ENSG00000309781 (HGNC:):

ENSG00000309781 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011810631).

BP6

Variant 20-58652112-C-A is Benign according to our data. Variant chr20-58652112-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 339043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 81 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STX16	NM_001001433.3	MANE Select	c.106C>A	p.Pro36Thr	missense	Exon 1 of 9	NP_001001433.1	O14662-1
STX16	NM_001134772.3		c.106C>A	p.Pro36Thr	missense	Exon 1 of 8	NP_001128244.1	O14662-5
STX16	NM_001204868.2		c.-54C>A		5_prime_UTR	Exon 2 of 10	NP_001191797.1	O14662-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STX16	ENST00000371141.8	TSL:2 MANE Select	c.106C>A	p.Pro36Thr	missense	Exon 1 of 9	ENSP00000360183.4	O14662-1
STX16	ENST00000358029.8	TSL:1	c.106C>A	p.Pro36Thr	missense	Exon 1 of 8	ENSP00000350723.4	O14662-5
STX16	ENST00000371132.8	TSL:1	c.81+25C>A		intron	N/A	ENSP00000360173.4	O14662-2

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000562

AC:

140

AN:

249004

AF XY:

0.000682

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.000907

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000920

AC:

1345

AN:

1461820

Hom.:

Cov.:

AF XY:

0.000946

AC XY:

688

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.0000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000951

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000187

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00109

AC:

1214

AN:

1111998

Other (OTH)

AF:

0.000530

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

155

233

310

388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000532

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41588

American (AMR)

AF:

0.0000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00187

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000941

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000724

Hom.:

Bravo

AF:

0.000442

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000659

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.00154

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Pseudohypoparathyroidism type 1B (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.023

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.077

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.80

M_CAP

Benign

0.0056

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

PhyloP100

2.1

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.20

REVEL

Benign

0.066

Sift

Benign

0.38

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.15

MVP

0.39

MPC

0.38

ClinPred

0.041

GERP RS

4.8

PromoterAI

-0.094

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.20

gMVP

0.47

Mutation Taster

=229/71

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over