rs1061064

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004782.4(SNAP29):c.18A>G(p.Lys6Lys) 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

Publications

23 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 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 Gene-Disease associations (from GenCC):

polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

PI4KA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 340830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.

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.18A>G	p.Lys6Lys	synonymous	Exon 1 of 5	NP_004773.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SNAP29	ENST00000215730.12	TSL:1 MANE Select	c.18A>G	p.Lys6Lys	synonymous	Exon 1 of 5	ENSP00000215730.6
SNAP29	ENST00000490458.1	TSL:2	n.48A>G		non_coding_transcript_exon	Exon 1 of 2
PI4KA	ENST00000449120.1	TSL:4	c.-24T>C		5_prime_UTR	Exon 1 of 4	ENSP00000402437.1

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

GnomAD2 exomes

AF:

0.515

AC:

116905

AN:

227086

AF XY:

0.527

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 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

African (AFR)

AF:

0.192

AC:

6425

AN:

33392

American (AMR)

AF:

0.411

AC:

17971

AN:

43714

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

13054

AN:

25772

East Asian (EAS)

AF:

0.442

AC:

17446

AN:

39508

South Asian (SAS)

AF:

0.603

AC:

51302

AN:

85082

European-Finnish (FIN)

AF:

0.702

AC:

36081

AN:

51366

Middle Eastern (MID)

AF:

0.501

AC:

2887

AN:

5760

European-Non Finnish (NFE)

AF:

0.550

AC:

608985

AN:

1107094

Other (OTH)

AF:

0.525

AC:

31520

AN:

60036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

16809

33618

50428

67237

84046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17018

34036

51054

68072

85090

<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:

0.447

AC:

67958

AN:

152054

Hom.:

17136

Cov.:

AF XY:

0.455

AC XY:

33835

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.206

AC:

8551

AN:

41506

American (AMR)

AF:

0.435

AC:

6659

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.504

AC:

1750

AN:

3472

East Asian (EAS)

AF:

0.417

AC:

2147

AN:

5148

South Asian (SAS)

AF:

0.587

AC:

2831

AN:

4824

European-Finnish (FIN)

AF:

0.712

AC:

7529

AN:

10580

Middle Eastern (MID)

AF:

0.476

AC:

139

AN:

292

European-Non Finnish (NFE)

AF:

0.545

AC:

37047

AN:

67924

Other (OTH)

AF:

0.438

AC:

923

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1825

3651

5476

7302

9127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.502

Hom.:

18138

Bravo

AF:

0.414

Asia WGS

AF:

0.483

AC:

1680

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

CEDNIK syndrome (4)

not provided (4)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.0

(source)

DANN

Benign

0.84

PhyloP100

0.26

PromoterAI

0.029

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over