chr22-20859092-C-T

Variant names:

• chr22-20859092-C-T
• rs1061063
• NM_004782.4:c.-19C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004782.4(SNAP29):​c.-19C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,574,152 control chromosomes in the GnomAD database, including 233,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19890 hom., cov: 33)
  • Exomes 𝑓: 0.55 (213963 hom.)
• Consequence: SNAP29 NM_004782.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.54
• Publications: 20 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 22-20859092-C-T is Benign according to our data. Variant chr22-20859092-C-T is described in ClinVar as Benign. ClinVar VariationId is 340826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.576 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.-19C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_004773.1	O95721
	SNAP29	NM_004782.4	MANE Select	c.-19C>T		5_prime_UTR	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.-19C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000215730.6	O95721
	SNAP29	ENST00000215730.12	TSL:1 MANE Select	c.-19C>T		5_prime_UTR	Exon 1 of 5	ENSP00000215730.6	O95721
	SNAP29	ENST00000880968.1		c.-19C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000551027.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76633 AN: 151960 Hom.: 19887 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.480

GnomAD2 exomes AF: 0.527 AC: 114504 AN: 217444 AF XY: 0.534

Gnomad AFR exome AF: 0.392

Gnomad AMR exome AF: 0.409

Gnomad ASJ exome AF: 0.516

Gnomad EAS exome AF: 0.407

Gnomad FIN exome AF: 0.706

Gnomad NFE exome AF: 0.547

Gnomad OTH exome AF: 0.523

GnomAD4 exome AF: 0.545 AC: 775737 AN: 1422074 Hom.: 213963 Cov.: 27 AF XY: 0.548 AC XY: 387858 AN XY: 707996

African (AFR) AF: 0.393 AC: 12969 AN: 32996

American (AMR) AF: 0.419 AC: 17889 AN: 42656

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 13257 AN: 25562

East Asian (EAS) AF: 0.442 AC: 17332 AN: 39208

South Asian (SAS) AF: 0.606 AC: 50794 AN: 83796

European-Finnish (FIN) AF: 0.701 AC: 35540 AN: 50676

Middle Eastern (MID) AF: 0.516 AC: 2927 AN: 5670

European-Non Finnish (NFE) AF: 0.548 AC: 593368 AN: 1082550

Other (OTH) AF: 0.537 AC: 31661 AN: 58960

GnomAD4 genome AF: 0.504 AC: 76672 AN: 152078 Hom.: 19890 Cov.: 33 AF XY: 0.511 AC XY: 38009 AN XY: 74358

African (AFR) AF: 0.403 AC: 16715 AN: 41496

American (AMR) AF: 0.455 AC: 6969 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1796 AN: 3470

East Asian (EAS) AF: 0.419 AC: 2162 AN: 5156

South Asian (SAS) AF: 0.595 AC: 2866 AN: 4820

European-Finnish (FIN) AF: 0.711 AC: 7526 AN: 10592

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.546 AC: 37094 AN: 67932

Other (OTH) AF: 0.482 AC: 1017 AN: 2112

Alfa AF: 0.520 Hom.: 18416

Bravo AF: 0.479

Asia WGS AF: 0.509 AC: 1771 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	CEDNIK syndrome (4)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.7
DANN	Benign	0.87
PhyloP100		-1.5
PromoterAI		-0.045	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=300/0	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: rs1061063; hg19: chr22-21213380;