rs737662

Variant names:

• chr22-38056358-C-G
• rs737662
• ENST00000445628.5:c.-470C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-38056358-C-G
• chr22-38056358-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000445628.5(PICK1):​c.-470C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,136 control chromosomes in the GnomAD database, including 7,549 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 (7546 hom., cov: 32)
  • Exomes 𝑓: 0.34 (3 hom.)
• Consequence: PICK1 ENST00000445628.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 11 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000445628.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICK1	ENST00000445628.5	TSL:4	c.-470C>G		5_prime_UTR	Exon 1 of 4	ENSP00000416487.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47348 AN: 151974 Hom.: 7537 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.341 AC: 15 AN: 44 Hom.: 3 Cov.: 0 AF XY: 0.395 AC XY: 15 AN XY: 38

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.412 AC: 14 AN: 34

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.312 AC: 47388 AN: 152092 Hom.: 7546 Cov.: 32 AF XY: 0.317 AC XY: 23536 AN XY: 74342

African (AFR) AF: 0.265 AC: 11015 AN: 41494

American (AMR) AF: 0.374 AC: 5712 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2061 AN: 5160

South Asian (SAS) AF: 0.379 AC: 1828 AN: 4818

European-Finnish (FIN) AF: 0.343 AC: 3625 AN: 10582

Middle Eastern (MID) AF: 0.279 AC: 81 AN: 290

European-Non Finnish (NFE) AF: 0.309 AC: 20997 AN: 67980

Other (OTH) AF: 0.318 AC: 672 AN: 2110

Alfa AF: 0.307 Hom.: 885

Bravo AF: 0.312

Asia WGS AF: 0.384 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.077
DANN	Benign	0.55
PhyloP100		-1.2
PromoterAI		-0.033	Neutral

Splicing

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

Other links and lift over

dbSNP: rs737662; hg19: chr22-38452365;