22-38060591-A-G

Variant summary

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

The NM_012407.4(PICK1):c.153+1246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,846 control chromosomes in the GnomAD database, including 7,648 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 (7648 hom., cov: 31)
• Consequence: PICK1 NM_012407.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICK1	NM_012407.4	c.153+1246A>G		intron_variant		ENST00000356976.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICK1	ENST00000356976.8	c.153+1246A>G		intron_variant		1	NM_012407.4	P1
	ENST00000445483.1	n.77-3074T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47542 AN: 151728 Hom.: 7640 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.325

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.313 AC: 47579 AN: 151846 Hom.: 7648 Cov.: 31 AF XY: 0.318 AC XY: 23557 AN XY: 74176

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.323

Alfa AF: 0.316 Hom.: 12859

Bravo AF: 0.313

Asia WGS AF: 0.378 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3952; hg19: chr22-38456598;