NM_001001433.3:c.-534C>G

Variant names:

• chr20-58651473-C-G
• rs190719996
• NM_001001433.3:c.-534C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001001433.3(STX16):​c.-534C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 154,334 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (0 hom.)
• Consequence: STX16 NM_001001433.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0220
• Publications: 0 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 20-58651473-C-G is Benign according to our data. Variant chr20-58651473-C-G is described in ClinVar as Benign. ClinVar VariationId is 339034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 188 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX16	NM_001001433.3	MANE Select	c.-534C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001001433.1	O14662-1
	STX16	NM_001001433.3	MANE Select	c.-534C>G		5_prime_UTR	Exon 1 of 9	NP_001001433.1	O14662-1
	STX16	NM_001134772.3		c.-534C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001128244.1	O14662-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX16	ENST00000371141.8	TSL:2 MANE Select	c.-534C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000360183.4	O14662-1
	STX16	ENST00000371141.8	TSL:2 MANE Select	c.-534C>G		5_prime_UTR	Exon 1 of 9	ENSP00000360183.4	O14662-1
	STX16-NPEPL1	ENST00000530122.1	TSL:5	n.-534C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 23	ENSP00000457522.1	H3BU86

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 188 AN: 152244 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.00304 AC: 6 AN: 1972 Hom.: 0 Cov.: 0 AF XY: 0.00309 AC XY: 4 AN XY: 1296

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10

East Asian (EAS) AF: 0.00 AC: 0 AN: 24

South Asian (SAS) AF: 0.00 AC: 0 AN: 564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00447 AC: 5 AN: 1118

Other (OTH) AF: 0.0128 AC: 1 AN: 78

GnomAD4 genome AF: 0.00123 AC: 188 AN: 152362 Hom.: 1 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74506

African (AFR) AF: 0.000553 AC: 23 AN: 41592

American (AMR) AF: 0.00229 AC: 35 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00187 AC: 127 AN: 68040

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00138 Hom.: 1

Bravo AF: 0.00127

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.2
DANN	Benign	0.43
PhyloP100		-0.022
PromoterAI		0.052	Neutral
Mutation Taster		=300/0	polymorphism

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: rs190719996; hg19: chr20-57226529;