22-20861118-GTTTTTT-GTTTTTTTTT

Variant names:

• chr22-20861118-G-GTTT
• rs362237
• NM_004782.4:c.237+1787_237+1789dupTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_004782.4(SNAP29):​c.237+1787_237+1789dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.011 (65 hom., cov: 0)
• Consequence: SNAP29 NM_004782.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 0 publications found

Genes affected

SNAP29 (HGNC:11133): (synaptosome associated protein 29) This gene, a member of the SNAP25 gene family, encodes a protein involved in multiple membrane trafficking steps. Two other members of this gene family, SNAP23 and SNAP25, encode proteins that bind a syntaxin protein and mediate synaptic vesicle membrane docking and fusion to the plasma membrane. The protein encoded by this gene binds tightly to multiple syntaxins and is localized to intracellular membrane structures rather than to the plasma membrane. While the protein is mostly membrane-bound, a significant fraction of it is found free in the cytoplasm. Use of multiple polyadenylation sites has been noted for this gene. [provided by RefSeq, Jul 2008]

SNAP29 Gene-Disease associations (from GenCC):

• CEDNIK syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0113 (1375/121788) while in subpopulation AFR AF = 0.0237 (733/30920). AF 95% confidence interval is 0.0223. There are 65 homozygotes in GnomAd4. There are 650 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP29	NM_004782.4	c.237+1787_237+1789dupTTT		intron_variant	Intron 1 of 4	ENST00000215730.12	NP_004773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNAP29	ENST00000215730.12	c.237+1771_237+1772insTTT		intron_variant	Intron 1 of 4	1	NM_004782.4	ENSP00000215730.6
SNAP29	ENST00000439214.1	c.-43+1478_-43+1479insTTT		intron_variant	Intron 1 of 4	3		ENSP00000411095.1
SNAP29	ENST00000490458.1	n.267+1771_267+1772insTTT		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1374 AN: 121788 Hom.: 65 Cov.: 0

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.00475

Gnomad AMR AF: 0.00854

Gnomad ASJ AF: 0.000310

Gnomad EAS AF: 0.00742

Gnomad SAS AF: 0.00218

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00761

Gnomad OTH AF: 0.00919

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0113 AC: 1375 AN: 121788 Hom.: 65 Cov.: 0 AF XY: 0.0113 AC XY: 650 AN XY: 57472

African (AFR) AF: 0.0237 AC: 733 AN: 30920

American (AMR) AF: 0.00854 AC: 97 AN: 11364

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 1 AN: 3230

East Asian (EAS) AF: 0.00745 AC: 29 AN: 3894

South Asian (SAS) AF: 0.00219 AC: 8 AN: 3660

European-Finnish (FIN) AF: 0.00499 AC: 28 AN: 5614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.00761 AC: 460 AN: 60416

Other (OTH) AF: 0.00917 AC: 15 AN: 1636

Alfa AF: 0.00443 Hom.: 281

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs362237; hg19: chr22-21215406;