NM_004782.4:c.18A>G

Variant names:

• chr22-20859128-A-G
• rs1061064
• NM_004782.4:c.18A>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.259
• Publications: 23 publications found

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]

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 Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

Sel.	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	O95721

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP29	ENST00000215730.12	TSL:1 MANE Select	c.18A>G	p.Lys6Lys	synonymous	Exon 1 of 5	ENSP00000215730.6	O95721
	SNAP29	ENST00000880968.1		c.18A>G	p.Lys6Lys	synonymous	Exon 1 of 5	ENSP00000551027.1
	SNAP29	ENST00000880966.1		c.18A>G	p.Lys6Lys	synonymous	Exon 2 of 6	ENSP00000551025.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67941 AN: 151936 Hom.: 17137 Cov.: 33

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

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.: 35 AF XY: 0.544 AC XY: 392734 AN XY: 721802

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

GnomAD4 genome AF: 0.447 AC: 67958 AN: 152054 Hom.: 17136 Cov.: 33 AF XY: 0.455 AC XY: 33835 AN XY: 74342

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

Alfa AF: 0.502 Hom.: 18138

Bravo AF: 0.414

Asia WGS AF: 0.483 AC: 1680 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	CEDNIK syndrome (4)
-	-	4	not provided (4)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.0
DANN	Benign	0.84
PhyloP100		0.26
PromoterAI		0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1061064; hg19: chr22-21213416; COSMIC: COSV53141857; COSMIC: COSV53141857;