chr22-20859128-A-G

Position:

chr22-20859128-A-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004782.4(SNAP29):c.18A>G(p.Lys6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,603,778 control chromosomes in the GnomAD database, including 234,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17136 hom., cov: 33)

Exomes 𝑓: 0.54 ( 216987 hom. )

Consequence

SNAP29
NM_004782.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.259

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:

PI4KA (HGNC:8983): (phosphatidylinositol 4-kinase alpha) This gene encodes a phosphatidylinositol (PI) 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. The protein encoded by this gene is a type III enzyme that is not inhibited by adenosine. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2018]

PI4KA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 22-20859128-A-G is Benign according to our data. Variant chr22-20859128-A-G is described in ClinVar as [Benign]. Clinvar id is 340830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-20859128-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.259 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP29	NM_004782.4 linkuse as main transcript	c.18A>G	p.Lys6=	synonymous_variant	1/5	ENST00000215730.12	NP_004773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SNAP29	ENST00000215730.12 linkuse as main transcript	c.18A>G	p.Lys6=	synonymous_variant	1/5	1	NM_004782.4	ENSP00000215730	P1
PI4KA	ENST00000449120.1 linkuse as main transcript	c.-24T>C		5_prime_UTR_variant	1/4	4		ENSP00000402437
SNAP29	ENST00000490458.1 linkuse as main transcript	n.48A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67941

AN:

151936

Hom.:

17137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.436

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.417

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.712

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.442

GnomAD3 exomes

AF:

0.515

AC:

116905

AN:

227086

Hom.:

31818

AF XY:

0.527

AC XY:

65509

AN XY:

124392

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.403

Gnomad ASJ exome

AF:

0.505

Gnomad EAS exome

AF:

0.410

Gnomad SAS exome

AF:

0.600

Gnomad FIN exome

AF:

0.709

Gnomad NFE exome

AF:

0.551

Gnomad OTH exome

AF:

0.518

GnomAD4 exome

AF:

0.541

AC:

785671

AN:

1451724

Hom.:

216987

Cov.:

AF XY:

0.544

AC XY:

392734

AN XY:

721802

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.411

Gnomad4 ASJ exome

AF:

0.507

Gnomad4 EAS exome

AF:

0.442

Gnomad4 SAS exome

AF:

0.603

Gnomad4 FIN exome

AF:

0.702

Gnomad4 NFE exome

AF:

0.550

Gnomad4 OTH exome

AF:

0.525

GnomAD4 genome

AF:

0.447

AC:

67958

AN:

152054

Hom.:

17136

Cov.:

AF XY:

0.455

AC XY:

33835

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.206

Gnomad4 AMR

AF:

0.435

Gnomad4 ASJ

AF:

0.504

Gnomad4 EAS

AF:

0.417

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.712

Gnomad4 NFE

AF:

0.545

Gnomad4 OTH

AF:

0.438

Alfa

AF:

0.503

Hom.:

13879

Bravo

AF:

0.414

Asia WGS

AF:

0.483

AC:

1680

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CEDNIK syndrome

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Jun 28, 2017	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, flagged submission

clinical testing

GeneDx

Jul 06, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.0

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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