20-58652105-C-A

Variant names:

• chr20-58652105-C-A
• NM_001001433.3:c.99C>A
• STX16 p.Thr33Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001001433.3(STX16):​c.99C>A​(p.Thr33Thr) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T33T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STX16 NM_001001433.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.59
• 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]

ENSG00000309781 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).

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.99C>A	p.Thr33Thr	synonymous	Exon 1 of 9	NP_001001433.1	O14662-1
	STX16	NM_001134772.3		c.99C>A	p.Thr33Thr	synonymous	Exon 1 of 8	NP_001128244.1	O14662-5
	STX16	NM_001204868.2		c.-61C>A		5_prime_UTR	Exon 2 of 10	NP_001191797.1	O14662-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX16	ENST00000371141.8	TSL:2 MANE Select	c.99C>A	p.Thr33Thr	synonymous	Exon 1 of 9	ENSP00000360183.4	O14662-1
	STX16	ENST00000358029.8	TSL:1	c.99C>A	p.Thr33Thr	synonymous	Exon 1 of 8	ENSP00000350723.4	O14662-5
	STX16	ENST00000371132.8	TSL:1	c.81+18C>A		intron	N/A	ENSP00000360173.4	O14662-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		6.6
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-57227161;