22-20861118-GTTTTTT-GTTTTTTTTT

Position:

• chr22-20861118-GTTTTTT-GTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_004782.4(SNAP29):​c.237+1787_237+1789dup 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

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 65 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP29	NM_004782.4	c.237+1787_237+1789dup		intron_variant		ENST00000215730.12	NP_004773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP29	ENST00000215730.12	c.237+1787_237+1789dup		intron_variant		1	NM_004782.4	ENSP00000215730	P1
SNAP29	ENST00000439214.1	c.-43+1494_-43+1496dup		intron_variant		3		ENSP00000411095
SNAP29	ENST00000490458.1	n.267+1787_267+1789dup		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.00854

Gnomad4 ASJ AF: 0.000310

Gnomad4 EAS AF: 0.00745

Gnomad4 SAS AF: 0.00219

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.00761

Gnomad4 OTH AF: 0.00917

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs362237; hg19: chr22-21215406;