chr22-20861118-GT-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_004782.4(SNAP29):​c.237+1789delT 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 0.0027 (1 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00271 (330/121810) while in subpopulation AFR AF = 0.00867 (268/30920). AF 95% confidence interval is 0.00781. There are 1 homozygotes in GnomAd4. There are 159 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00268 AC: 327 AN: 121810 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00858

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000616

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000512

Gnomad SAS AF: 0.000544

Gnomad FIN AF: 0.00178

Gnomad MID AF: 0.00439

Gnomad NFE AF: 0.000629

Gnomad OTH AF: 0.00123

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

GnomAD4 genome AF: 0.00271 AC: 330 AN: 121810 Hom.: 1 Cov.: 0 AF XY: 0.00277 AC XY: 159 AN XY: 57478

African (AFR) AF: 0.00867 AC: 268 AN: 30920

American (AMR) AF: 0.000616 AC: 7 AN: 11370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3230

East Asian (EAS) AF: 0.000514 AC: 2 AN: 3894

South Asian (SAS) AF: 0.000546 AC: 2 AN: 3660

European-Finnish (FIN) AF: 0.00178 AC: 10 AN: 5610

Middle Eastern (MID) AF: 0.00472 AC: 1 AN: 212

European-Non Finnish (NFE) AF: 0.000629 AC: 38 AN: 60436

Other (OTH) AF: 0.00122 AC: 2 AN: 1636

Alfa AF: 0.000651 Hom.: 281

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

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;