22-20881101-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004782.4(SNAP29):c.487A>G(p.Ser163Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0058 in 1,612,848 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 69 hom. )

Consequence

SNAP29
NM_004782.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.47

Publications

14 publications found

Variant links:

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

SNAP29 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051186383).

BP6

Variant 22-20881101-A-G is Benign according to our data. Variant chr22-20881101-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00593 (903/152374) while in subpopulation EAS AF = 0.0551 (286/5188). AF 95% confidence interval is 0.0499. There are 8 homozygotes in GnomAd4. There are 424 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

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.487A>G	p.Ser163Gly	missense	Exon 3 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.487A>G	p.Ser163Gly	missense	Exon 3 of 5	ENSP00000215730.6
	SNAP29	ENST00000439214.1	TSL:3	c.208A>G	p.Ser70Gly	missense	Exon 3 of 5	ENSP00000411095.1

Frequencies

GnomAD3 genomes

AF:

0.00596

AC:

907

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0554

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00535

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00736

AC:

1850

AN:

251378

AF XY:

0.00725

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.00361

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0560

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00481

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.00579

AC:

8450

AN:

1460474

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

4184

AN XY:

726690

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

33468

American (AMR)

AF:

0.00373

AC:

167

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000498

AC:

AN:

26128

East Asian (EAS)

AF:

0.0465

AC:

1846

AN:

39684

South Asian (SAS)

AF:

0.00182

AC:

157

AN:

86230

European-Finnish (FIN)

AF:

0.00174

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00516

AC:

5728

AN:

1110714

Other (OTH)

AF:

0.00633

AC:

382

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

361

723

1084

1446

1807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

224

448

672

896

1120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00593

AC:

903

AN:

152374

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

424

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00216

AC:

AN:

41594

American (AMR)

AF:

0.00765

AC:

117

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.0551

AC:

286

AN:

5188

South Asian (SAS)

AF:

0.00249

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00169

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00535

AC:

364

AN:

68042

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

135

180

225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00635

Hom.:

Bravo

AF:

0.00658

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.00713

AC:

866

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.00523

EpiControl

AF:

0.00545

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Dec 23, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19350501)

Jul 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SNAP29: BP4, BS1, BS2

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CEDNIK syndrome

Benign:2

Mar 31, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

PhyloP100

6.5

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.2

REVEL

Benign

0.17

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.015

Polyphen

0.78

Vest4

0.48

MVP

0.65

MPC

0.098

ClinPred

0.037

GERP RS

4.8

Varity_R

0.21

gMVP

0.37

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over