rs713729

Positions:

• chr22-38059462-T-A

Variant summary

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

The NM_012407.4(PICK1):​c.153+117T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 759,668 control chromosomes in the GnomAD database, including 24,602 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 0.20 (4036 hom., cov: 32)
  • Exomes 𝑓: 0.25 (20566 hom.)
• Consequence: PICK1 NM_012407.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PICK1	NM_012407.4	c.153+117T>A		intron_variant		ENST00000356976.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PICK1	ENST00000356976.8	c.153+117T>A		intron_variant		1	NM_012407.4	P1
	ENST00000445483.1	n.77-1945A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30997 AN: 152098 Hom.: 4033 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.252 AC: 153297 AN: 607452 Hom.: 20566 AF XY: 0.249 AC XY: 79937 AN XY: 320392

Gnomad4 AFR exome AF: 0.0518

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.329

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.204 AC: 31002 AN: 152216 Hom.: 4036 Cov.: 32 AF XY: 0.204 AC XY: 15222 AN XY: 74444

Gnomad4 AFR AF: 0.0544

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.204

Alfa AF: 0.242 Hom.: 640

Bravo AF: 0.187

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs713729; hg19: chr22-38455469;