NM_001001433.3:c.557-461C>T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX16	NM_001001433.3	c.557-461C>T		intron_variant	Intron 5 of 8	ENST00000371141.8	NP_001001433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX16	ENST00000371141.8	c.557-461C>T		intron_variant	Intron 5 of 8	2	NM_001001433.3	ENSP00000360183.4
STX16-NPEPL1	ENST00000530122.1	n.557-461C>T		intron_variant	Intron 5 of 22	5		ENSP00000457522.1

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

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.503

Alfa AF: 0.523 Hom.: 2527

Bravo AF: 0.501

Asia WGS AF: 0.496 AC: 1725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.1
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs6100158; hg19: chr20-57245107;