chr22-20861118-G-GTT

Variant names:

• chr22-20861118-G-GTT
• rs362237
• NM_004782.4:c.237+1788_237+1789dupTT

Variant summary

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

The NM_004782.4(SNAP29):​c.237+1788_237+1789dupTT 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 0.37 (9026 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 (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNAP29	NM_004782.4	c.237+1788_237+1789dupTT		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+1772insTT		intron_variant	Intron 1 of 4	1	NM_004782.4	ENSP00000215730.6
SNAP29	ENST00000439214.1	c.-43+1478_-43+1479insTT		intron_variant	Intron 1 of 4	3		ENSP00000411095.1
SNAP29	ENST00000490458.1	n.267+1771_267+1772insTT		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.368 AC: 44713 AN: 121552 Hom.: 9027 Cov.: 0

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.368 AC: 44707 AN: 121552 Hom.: 9026 Cov.: 0 AF XY: 0.359 AC XY: 20596 AN XY: 57336

African (AFR) AF: 0.295 AC: 9117 AN: 30882

American (AMR) AF: 0.437 AC: 4947 AN: 11324

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1370 AN: 3226

East Asian (EAS) AF: 0.480 AC: 1864 AN: 3886

South Asian (SAS) AF: 0.333 AC: 1211 AN: 3640

European-Finnish (FIN) AF: 0.143 AC: 798 AN: 5592

Middle Eastern (MID) AF: 0.390 AC: 82 AN: 210

European-Non Finnish (NFE) AF: 0.401 AC: 24188 AN: 60314

Other (OTH) AF: 0.400 AC: 655 AN: 1636

Alfa AF: 0.152 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

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

Other links and lift over

dbSNP: rs362237; hg19: chr22-21215406; COSMIC: COSV53142773; COSMIC: COSV53142773;