rs11089858

Positions:

• chr22-38057128-G-A
• chr22-38057128-G-T

Variant summary

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

The ENST00000445628.5(PICK1):​c.-229-137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0706 in 153,180 control chromosomes in the GnomAD database, including 748 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 0.071 (748 hom., cov: 33)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: PICK1 ENST00000445628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.901

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 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.-229-137G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0708 AC: 10769 AN: 152184 Hom.: 747 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0643

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0568

GnomAD4 exome AF: 0.0205 AC: 18 AN: 878 Hom.: 0 AF XY: 0.0226 AC XY: 12 AN XY: 530

Gnomad4 AMR exome AF: 0.0169

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.0203

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0141

Gnomad4 OTH exome AF: 0.0667

GnomAD4 genome AF: 0.0709 AC: 10800 AN: 152302 Hom.: 748 Cov.: 33 AF XY: 0.0702 AC XY: 5230 AN XY: 74450

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.0355

Gnomad4 ASJ AF: 0.0355

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0636

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.0233

Gnomad4 OTH AF: 0.0595

Alfa AF: 0.0441 Hom.: 50

Bravo AF: 0.0771

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11089858; hg19: chr22-38453135;