22-38060591-A-G

Variant names:

• chr22-38060591-A-G
• rs3952
• NM_012407.4:c.153+1246A>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.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
• Publications: 31 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 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.153+1246A>G		intron	N/A	NP_036539.1
	PICK1	NM_001039583.1		c.153+1246A>G		intron	N/A	NP_001034672.1
	PICK1	NM_001039584.1		c.153+1246A>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.153+1246A>G		intron	N/A	ENSP00000349465.3
	PICK1	ENST00000951428.1		c.153+1246A>G		intron	N/A	ENSP00000621487.1
	PICK1	ENST00000951430.1		c.153+1246A>G		intron	N/A	ENSP00000621489.1

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

African (AFR) AF: 0.262 AC: 10844 AN: 41408

American (AMR) AF: 0.373 AC: 5695 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3472

East Asian (EAS) AF: 0.403 AC: 2075 AN: 5150

South Asian (SAS) AF: 0.381 AC: 1829 AN: 4800

European-Finnish (FIN) AF: 0.342 AC: 3601 AN: 10520

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.314 AC: 21311 AN: 67918

Other (OTH) AF: 0.323 AC: 682 AN: 2112

Alfa AF: 0.316 Hom.: 29921

Bravo AF: 0.313

Asia WGS AF: 0.378 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3952; hg19: chr22-38456598;