22-20861118-GTTTTTT-GTTTTTTTTTT

Variant names:

• chr22-20861118-G-GTTTT
• rs362237
• NM_004782.4:c.237+1786_237+1789dupTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004782.4(SNAP29):​c.237+1786_237+1789dupTTTT 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 0.00025 (2 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP29	NM_004782.4	c.237+1786_237+1789dupTTTT		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+1772insTTTT		intron_variant	Intron 1 of 4	1	NM_004782.4	ENSP00000215730.6
SNAP29	ENST00000439214.1	c.-43+1478_-43+1479insTTTT		intron_variant	Intron 1 of 4	3		ENSP00000411095.1
SNAP29	ENST00000490458.1	n.267+1771_267+1772insTTTT		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.000254 AC: 31 AN: 121808 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.000453

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000176

Gnomad ASJ AF: 0.000310

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000215

Gnomad OTH AF: 0.000613

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

GnomAD4 genome AF: 0.000254 AC: 31 AN: 121808 Hom.: 2 Cov.: 0 AF XY: 0.000278 AC XY: 16 AN XY: 57484

African (AFR) AF: 0.000453 AC: 14 AN: 30920

American (AMR) AF: 0.000176 AC: 2 AN: 11368

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3894

South Asian (SAS) AF: 0.00 AC: 0 AN: 3660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5612

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

European-Non Finnish (NFE) AF: 0.000215 AC: 13 AN: 60434

Other (OTH) AF: 0.000611 AC: 1 AN: 1636

Alfa AF: 0.00 Hom.: 281

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

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;