Variant 22-20888256-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.136

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP29	NM_004782.4 link	c.*420A>G		3_prime_UTR_variant	5/5	ENST00000215730.12	NP_004773.1	O95721

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNAP29	ENST00000215730.12 link	c.*420A>G		3_prime_UTR_variant	5/5	1	NM_004782.4	ENSP00000215730.6		O95721

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58166

AN:

150328

Hom.:

11710

Cov.:

show subpopulations

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.:

AF XY:

0.328

AC XY:

24549

AN XY:

74800

show subpopulations

Gnomad4 AFR exome

AF:

0.467

Gnomad4 AMR exome

AF:

0.458

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.486

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.330

Gnomad4 OTH exome

AF:

0.332

GnomAD4 genome

AF:

0.387

AC:

58234

AN:

150444

Hom.:

11731

Cov.:

AF XY:

0.382

AC XY:

28059

AN XY:

73420

show subpopulations

Gnomad4 AFR

AF:

0.474

Gnomad4 AMR

AF:

0.453

Gnomad4 ASJ

AF:

0.399

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.302

Gnomad4 FIN

AF:

0.213

Gnomad4 NFE

AF:

0.342

Gnomad4 OTH

AF:

0.410

Alfa

AF:

0.377

Hom.:

3982

Bravo

AF:

0.412

Asia WGS

AF:

0.389

AC:

1351

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CEDNIK syndrome

Benign:1

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.2

DANN

Benign

0.75

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