22-38067645-T-G

Variant names:

• chr22-38067645-T-G
• rs2076369
• NM_012407.4:c.283-59T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 25 publications found

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 Gene-Disease associations (from GenCC):

• male infertility due to globozoospermia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000233739 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012407.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICK1	NM_012407.4	MANE Select	c.283-59T>G		intron	N/A	NP_036539.1
	PICK1	NM_001039583.1		c.283-59T>G		intron	N/A	NP_001034672.1
	PICK1	NM_001039584.1		c.283-59T>G		intron	N/A	NP_001034673.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICK1	ENST00000356976.8	TSL:1 MANE Select	c.283-59T>G		intron	N/A	ENSP00000349465.3
	PICK1	ENST00000494434.1	TSL:4	n.169T>G		non_coding_transcript_exon	Exon 1 of 5
	PICK1	ENST00000404072.7	TSL:2	c.283-59T>G		intron	N/A	ENSP00000385205.3

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

African (AFR) AF: 0.927 AC: 28408 AN: 30630

American (AMR) AF: 0.650 AC: 28836 AN: 44354

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 14239 AN: 25232

East Asian (EAS) AF: 0.642 AC: 25010 AN: 38956

South Asian (SAS) AF: 0.630 AC: 52610 AN: 83452

European-Finnish (FIN) AF: 0.722 AC: 38098 AN: 52742

Middle Eastern (MID) AF: 0.597 AC: 3263 AN: 5466

European-Non Finnish (NFE) AF: 0.623 AC: 613094 AN: 983680

Other (OTH) AF: 0.643 AC: 35794 AN: 55684

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

African (AFR) AF: 0.918 AC: 38138 AN: 41530

American (AMR) AF: 0.640 AC: 9787 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1980 AN: 3472

East Asian (EAS) AF: 0.703 AC: 3618 AN: 5148

South Asian (SAS) AF: 0.616 AC: 2967 AN: 4818

European-Finnish (FIN) AF: 0.726 AC: 7684 AN: 10584

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41906 AN: 67938

Other (OTH) AF: 0.660 AC: 1393 AN: 2110

Alfa AF: 0.662 Hom.: 55703

Bravo AF: 0.715

Asia WGS AF: 0.660 AC: 2297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.36
DANN	Benign	0.70
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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