chr22-20859121-A-G

Position:

chr22-20859121-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004782.4(SNAP29):c.11A>G(p.Tyr4Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,606,626 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SNAP29
NM_004782.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNAP29	NM_004782.4 linkuse as main transcript	c.11A>G	p.Tyr4Cys	missense_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.11A>G	p.Tyr4Cys	missense_variant	1/5	1	NM_004782.4	ENSP00000215730	P1
PI4KA	ENST00000449120.1 linkuse as main transcript	c.-19+2T>C		splice_donor_variant		4		ENSP00000402437
SNAP29	ENST00000490458.1 linkuse as main transcript	n.41A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000876

AC:

AN:

228258

Hom.:

AF XY:

0.00000799

AC XY:

AN XY:

125192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1454586

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

723198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2022

The c.11A>G (p.Y4C) alteration is located in exon 1 (coding exon 1) of the SNAP29 gene. This alteration results from a A to G substitution at nucleotide position 11, causing the tyrosine (Y) at amino acid position 4 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.0047

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.81

M_CAP

Benign

0.077

MetaRNN

Uncertain

0.55

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.17

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.53

MutPred

0.19

Loss of phosphorylation at Y4 (P = 0.0861);

MVP

0.52

MPC

0.31

ClinPred

0.97

GERP RS

0.56

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.29

gMVP

0.64

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