22-38067645-T-G

Position:

• chr22-38067645-T-G

Variant summary

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

The NM_012407.4(PICK1):​c.283-59T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,472,282 control chromosomes in the GnomAD database, including 309,604 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 0.71 (39817 hom., cov: 32)
  • Exomes 𝑓: 0.64 (269787 hom.)
• Consequence: PICK1 NM_012407.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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]

PICK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PICK1	NM_012407.4	c.283-59T>G		intron_variant		ENST00000356976.8	NP_036539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PICK1	ENST00000356976.8	c.283-59T>G		intron_variant		1	NM_012407.4	ENSP00000349465.3

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107993 AN: 151968 Hom.: 39761 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.659

GnomAD4 exome AF: 0.636 AC: 839352 AN: 1320196 Hom.: 269787 Cov.: 19 AF XY: 0.634 AC XY: 420266 AN XY: 663398

Gnomad4 AFR exome AF: 0.927

Gnomad4 AMR exome AF: 0.650

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.642

Gnomad4 SAS exome AF: 0.630

Gnomad4 FIN exome AF: 0.722

Gnomad4 NFE exome AF: 0.623

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome AF: 0.711 AC: 108118 AN: 152086 Hom.: 39817 Cov.: 32 AF XY: 0.711 AC XY: 52885 AN XY: 74332

Gnomad4 AFR AF: 0.918

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.660

Alfa AF: 0.647 Hom.: 4937

Bravo AF: 0.715

Asia WGS AF: 0.660 AC: 2297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.36
DANN	Benign	0.70

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: rs2076369; hg19: chr22-38463652; COSMIC: COSV63659720; COSMIC: COSV63659720;