dbSNP rs11089858: PICK1:c.-229-137G>A (chr22-38057128-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000445628.5(PICK1):c.-229-137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0706 in 153,180 control chromosomes in the GnomAD database, including 748 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 0.071 ( 748 hom., cov: 33)

Exomes 𝑓: 0.021 ( 0 hom. )

Consequence

PICK1
ENST00000445628.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.901

Publications

4 publications found

Variant links:

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

PICK1 links:

ENSG00000233739 (HGNC:):

ENSG00000233739 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICK1	NM_001039583.1		c.-419G>A		upstream_gene	N/A	NP_001034672.1
	PICK1	NM_001039584.1		c.-366G>A		upstream_gene	N/A	NP_001034673.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PICK1	ENST00000445628.5	TSL:4	c.-229-137G>A	intron	N/A	ENSP00000416487.1
PICK1	ENST00000404072.7	TSL:2	c.-419G>A	upstream_gene	N/A	ENSP00000385205.3
PICK1	ENST00000951426.1		c.-419G>A	upstream_gene	N/A	ENSP00000621485.1

Frequencies

GnomAD3 genomes

AF:

0.0708

AC:

10769

AN:

152184

Hom.:

747

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0353

Gnomad ASJ

AF:

0.0355

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.0643

Gnomad FIN

AF:

0.0417

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0233

Gnomad OTH

AF:

0.0568

GnomAD4 exome

AF:

0.0205

AC:

AN:

878

Hom.:

AF XY:

0.0226

AC XY:

AN XY:

530

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.0169

AC:

AN:

118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.0203

AC:

AN:

148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0141

AC:

AN:

568

Other (OTH)

AF:

0.0667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0709

AC:

10800

AN:

152302

Hom.:

748

Cov.:

AF XY:

0.0702

AC XY:

5230

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.170

AC:

7052

AN:

41550

American (AMR)

AF:

0.0355

AC:

544

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0355

AC:

123

AN:

3468

East Asian (EAS)

AF:

0.112

AC:

582

AN:

5176

South Asian (SAS)

AF:

0.0636

AC:

307

AN:

4830

European-Finnish (FIN)

AF:

0.0417

AC:

443

AN:

10618

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0233

AC:

1585

AN:

68028

Other (OTH)

AF:

0.0595

AC:

126

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

491

983

1474

1966

2457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0441

Hom.:

Bravo

AF:

0.0771

Asia WGS

AF:

0.0850

AC:

297

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.90

PromoterAI

0.022

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over