22-20881101-A-G

Position:

chr22-20881101-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000215730.12(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
ENST00000215730.12 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.47

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 235285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-20881101-A-G is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP29	NM_004782.4 linkuse as main transcript	c.487A>G	p.Ser163Gly	missense_variant	3/5	ENST00000215730.12	NP_004773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP29	ENST00000215730.12 linkuse as main transcript	c.487A>G	p.Ser163Gly	missense_variant	3/5	1	NM_004782.4	ENSP00000215730	P1
SNAP29	ENST00000439214.1 linkuse as main transcript	c.208A>G	p.Ser70Gly	missense_variant	3/5	3		ENSP00000411095

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

GnomAD3 exomes

AF:

0.00736

AC:

1850

AN:

251378

Hom.:

AF XY:

0.00725

AC XY:

985

AN XY:

135860

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 SAS exome

AF:

0.00170

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

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00373

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.0465

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00516

Gnomad4 OTH exome

AF:

0.00633

GnomAD4 genome

AF:

0.00593

AC:

903

AN:

152374

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

424

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00216

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0551

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00535

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00642

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	This variant is associated with the following publications: (PMID: 19350501) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	SNAP29: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 23, 2015	- -

CEDNIK syndrome

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Mar 31, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

T;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.78

P;.

Vest4

0.48

MVP

0.65

MPC

0.098

ClinPred

0.037

GERP RS

4.8

Varity_R

0.21

gMVP

0.37

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over