Genetic Variant STX16:c.-355C>T (chr20-58651652-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001001433.3(STX16):c.-355C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 238,992 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

STX16
NM_001001433.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.133

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 20-58651652-C-T is Benign according to our data. Variant chr20-58651652-C-T is described in ClinVar as Benign. ClinVar VariationId is 339039.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 354 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	Effect	Exon Rank	Protein	UniProt
STX16	NM_001001433.3	MANE Select	c.-355C>T	5_prime_UTR	Exon 1 of 9	NP_001001433.1	O14662-1
STX16	NM_001134772.3		c.-355C>T	5_prime_UTR	Exon 1 of 8	NP_001128244.1	O14662-5
STX16	NM_001134773.3		c.-355C>T	5_prime_UTR	Exon 1 of 9	NP_001128245.1	O14662-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STX16	ENST00000371141.8	TSL:2 MANE Select	c.-355C>T	5_prime_UTR	Exon 1 of 9	ENSP00000360183.4	O14662-1
STX16	ENST00000371132.8	TSL:1	c.-355C>T	5_prime_UTR	Exon 1 of 8	ENSP00000360173.4	O14662-2
STX16-NPEPL1	ENST00000530122.1	TSL:5	n.-355C>T	non_coding_transcript_exon	Exon 1 of 23	ENSP00000457522.1	H3BU86

Frequencies

GnomAD3 genomes

AF:

0.00231

AC:

351

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00813

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.000300

AC:

AN:

86702

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

AN XY:

46560

show subpopulations

African (AFR)

AF:

0.00755

AC:

AN:

2518

American (AMR)

AF:

0.000947

AC:

AN:

4222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2048

East Asian (EAS)

AF:

0.00

AC:

AN:

4002

South Asian (SAS)

AF:

0.00

AC:

AN:

15028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

326

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

50466

Other (OTH)

AF:

0.000459

AC:

AN:

4358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00232

AC:

354

AN:

152290

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

176

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00818

AC:

340

AN:

41550

American (AMR)

AF:

0.000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00245

Hom.:

Bravo

AF:

0.00283

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Pseudohypoparathyroidism type 1B (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

0.13

PromoterAI

-0.012

Neutral

(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