chr22-20888256-A-G

Variant names:

• chr22-20888256-A-G
• rs178077
• NM_004782.4:c.*420A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004782.4(SNAP29):​c.*420A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 287,798 control chromosomes in the GnomAD database, including 19,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11731 hom., cov: 29)
  • Exomes 𝑓: 0.33 (8208 hom.)
• Consequence: SNAP29 NM_004782.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.136
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 22-20888256-A-G is Benign according to our data. Variant chr22-20888256-A-G is described in ClinVar as Benign. ClinVar VariationId is 340842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004782.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP29	NM_004782.4	MANE Select	c.*420A>G		3_prime_UTR	Exon 5 of 5	NP_004773.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP29	ENST00000215730.12	TSL:1 MANE Select	c.*420A>G		3_prime_UTR	Exon 5 of 5	ENSP00000215730.6

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58166 AN: 150328 Hom.: 11710 Cov.: 29

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.331 AC: 45437 AN: 137354 Hom.: 8208 Cov.: 0 AF XY: 0.328 AC XY: 24549 AN XY: 74800

African (AFR) AF: 0.467 AC: 1622 AN: 3472

American (AMR) AF: 0.458 AC: 2237 AN: 4886

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1236 AN: 3182

East Asian (EAS) AF: 0.486 AC: 2615 AN: 5382

South Asian (SAS) AF: 0.278 AC: 6725 AN: 24208

European-Finnish (FIN) AF: 0.219 AC: 1471 AN: 6720

Middle Eastern (MID) AF: 0.344 AC: 167 AN: 486

European-Non Finnish (NFE) AF: 0.330 AC: 27131 AN: 82300

Other (OTH) AF: 0.332 AC: 2233 AN: 6718

GnomAD4 genome AF: 0.387 AC: 58234 AN: 150444 Hom.: 11731 Cov.: 29 AF XY: 0.382 AC XY: 28059 AN XY: 73420

African (AFR) AF: 0.474 AC: 19325 AN: 40748

American (AMR) AF: 0.453 AC: 6822 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1379 AN: 3458

East Asian (EAS) AF: 0.489 AC: 2497 AN: 5102

South Asian (SAS) AF: 0.302 AC: 1428 AN: 4722

European-Finnish (FIN) AF: 0.213 AC: 2202 AN: 10322

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23139 AN: 67742

Other (OTH) AF: 0.410 AC: 856 AN: 2090

Alfa AF: 0.374 Hom.: 6332

Bravo AF: 0.412

Asia WGS AF: 0.389 AC: 1351 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	CEDNIK syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.75
PhyloP100		-0.14
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: rs178077; hg19: chr22-21242544; COSMIC: COSV53143438; COSMIC: COSV53143438;