22-20861118-GTTTTTT-GTTTTTTT

Variant names:

• chr22-20861118-G-GT
• rs362237
• NM_004782.4:c.237+1789dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004782.4(SNAP29):​c.237+1789dupT 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 0.12 (3057 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.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP29	NM_004782.4	c.237+1789dupT		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+1772insT		intron_variant	Intron 1 of 4	1	NM_004782.4	ENSP00000215730.6
SNAP29	ENST00000439214.1	c.-43+1478_-43+1479insT		intron_variant	Intron 1 of 4	3		ENSP00000411095.1
SNAP29	ENST00000490458.1	n.267+1771_267+1772insT		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 14767 AN: 121750 Hom.: 3057 Cov.: 0

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.00119

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0183

Gnomad EAS AF: 0.0576

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0968

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

GnomAD4 genome AF: 0.121 AC: 14772 AN: 121750 Hom.: 3057 Cov.: 0 AF XY: 0.121 AC XY: 6928 AN XY: 57454

African (AFR) AF: 0.413 AC: 12738 AN: 30872

American (AMR) AF: 0.0559 AC: 635 AN: 11366

Ashkenazi Jewish (ASJ) AF: 0.0183 AC: 59 AN: 3228

East Asian (EAS) AF: 0.0573 AC: 223 AN: 3892

South Asian (SAS) AF: 0.0224 AC: 82 AN: 3660

European-Finnish (FIN) AF: 0.0135 AC: 76 AN: 5610

Middle Eastern (MID) AF: 0.0566 AC: 12 AN: 212

European-Non Finnish (NFE) AF: 0.0130 AC: 784 AN: 60432

Other (OTH) AF: 0.0990 AC: 162 AN: 1636

Alfa AF: 0.00352 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 (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: rs362237; hg19: chr22-21215406;