chr22-38056475-G-A

Position:

• chr22-38056475-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000445628.5(PICK1):​c.-353G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,068 control chromosomes in the GnomAD database, including 8,685 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8683 hom., cov: 32)
  • Exomes 𝑓: 0.31 (2 hom.)
• Consequence: PICK1 ENST00000445628.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

Genes affected

PICK1 (HGNC:9394): (protein interacting with PRKCA 1) The protein encoded by this gene contains a PDZ domain, through which it interacts with protein kinase C, alpha (PRKCA). This protein may function as an adaptor that binds to and organizes the subcellular localization of a variety of membrane proteins. It has been shown to interact with multiple glutamate receptor subtypes, monoamine plasma membrane transporters, as well as non-voltage gated sodium channels, and may target PRKCA to these membrane proteins and thus regulate their distribution and function. This protein has also been found to act as an anchoring protein that specifically targets PRKCA to mitochondria in a ligand-specific manner. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICK1	ENST00000445628.5	c.-353G>A		5_prime_UTR_variant	1/4	4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50849 AN: 151914 Hom.: 8670 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.306 AC: 11 AN: 36 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 8 AN XY: 32

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.335 AC: 50898 AN: 152032 Hom.: 8683 Cov.: 32 AF XY: 0.339 AC XY: 25161 AN XY: 74294

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.332

Alfa AF: 0.321 Hom.: 977

Bravo AF: 0.338

Asia WGS AF: 0.390 AC: 1359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3026682; hg19: chr22-38452482; COSMIC: COSV63661157;