rs737662

Positions:

• chr22-38056358-C-G
• chr22-38056358-C-T

Variant summary

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

The ENST00000445628.5(PICK1):​c.-470C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,136 control chromosomes in the GnomAD database, including 7,549 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 0.31 (7546 hom., cov: 32)
  • Exomes 𝑓: 0.34 (3 hom.)
• Consequence: PICK1 ENST00000445628.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.88).
• 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.-470C>G		5_prime_UTR_variant	1/4	4

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47348 AN: 151974 Hom.: 7537 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.341 AC: 15 AN: 44 Hom.: 3 Cov.: 0 AF XY: 0.395 AC XY: 15 AN XY: 38

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.312 AC: 47388 AN: 152092 Hom.: 7546 Cov.: 32 AF XY: 0.317 AC XY: 23536 AN XY: 74342

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.318

Alfa AF: 0.307 Hom.: 885

Bravo AF: 0.312

Asia WGS AF: 0.384 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.077
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs737662; hg19: chr22-38452365;