rs41296205

Variant names:

• chr20-58651657-C-A
• rs41296205
• NM_001001433.3:c.-350C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-58651657-C-A
• chr20-58651657-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001001433.3(STX16):​c.-350C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 251,442 control chromosomes in the GnomAD database, including 531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (276 hom., cov: 32)
  • Exomes 𝑓: 0.065 (255 hom.)
• Consequence: STX16 NM_001001433.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.722
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-58651657-C-A is Benign according to our data. Variant chr20-58651657-C-A is described in ClinVar as Benign. ClinVar VariationId is 339040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.

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.-350C>A		5_prime_UTR	Exon 1 of 9	NP_001001433.1	O14662-1
	STX16	NM_001134772.3		c.-350C>A		5_prime_UTR	Exon 1 of 8	NP_001128244.1	O14662-5
	STX16	NM_001134773.3		c.-350C>A		5_prime_UTR	Exon 1 of 9	NP_001128245.1	O14662-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX16	ENST00000371141.8	TSL:2 MANE Select	c.-350C>A		5_prime_UTR	Exon 1 of 9	ENSP00000360183.4	O14662-1
	STX16	ENST00000371132.8	TSL:1	c.-350C>A		5_prime_UTR	Exon 1 of 8	ENSP00000360173.4	O14662-2
	STX16-NPEPL1	ENST00000530122.1	TSL:5	n.-350C>A		non_coding_transcript_exon	Exon 1 of 23	ENSP00000457522.1	H3BU86

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7802 AN: 152184 Hom.: 275 Cov.: 32

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0594

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0662

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0712

Gnomad OTH AF: 0.0622

GnomAD4 exome AF: 0.0654 AC: 6481 AN: 99140 Hom.: 255 Cov.: 0 AF XY: 0.0645 AC XY: 3428 AN XY: 53174

African (AFR) AF: 0.0165 AC: 50 AN: 3022

American (AMR) AF: 0.0599 AC: 277 AN: 4626

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 156 AN: 2352

East Asian (EAS) AF: 0.000438 AC: 2 AN: 4564

South Asian (SAS) AF: 0.0651 AC: 1118 AN: 17178

European-Finnish (FIN) AF: 0.0663 AC: 283 AN: 4270

Middle Eastern (MID) AF: 0.0532 AC: 20 AN: 376

European-Non Finnish (NFE) AF: 0.0736 AC: 4250 AN: 57714

Other (OTH) AF: 0.0645 AC: 325 AN: 5038

GnomAD4 genome AF: 0.0512 AC: 7802 AN: 152302 Hom.: 276 Cov.: 32 AF XY: 0.0517 AC XY: 3848 AN XY: 74470

African (AFR) AF: 0.0161 AC: 671 AN: 41572

American (AMR) AF: 0.0593 AC: 907 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.0661 AC: 319 AN: 4828

European-Finnish (FIN) AF: 0.0577 AC: 612 AN: 10612

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0712 AC: 4841 AN: 68016

Other (OTH) AF: 0.0639 AC: 135 AN: 2112

Alfa AF: 0.0552 Hom.: 142

Bravo AF: 0.0500

Asia WGS AF: 0.0350 AC: 120 AN: 3478

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	-0.82
CADD	Benign	2.2
DANN	Benign	0.87
PhyloP100		-0.72
PromoterAI		-0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs41296205; hg19: chr20-57226713;