Variant 22-38075140-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_012407.4(PICK1):c.*8G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,605,782 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00076 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 44 hom. )

Consequence

PICK1
NM_012407.4 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.447

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 links:

PICK1 (HGNC:):

PICK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 22-38075140-G-A is Benign according to our data. Variant chr22-38075140-G-A is described in ClinVar as [Benign]. Clinvar id is 3044049.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000762 (116/152204) while in subpopulation SAS AF= 0.023 (111/4820). AF 95% confidence interval is 0.0196. There are 5 homozygotes in gnomad4. There are 79 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PICK1	NM_012407.4 linkuse as main transcript	c.*8G>A		3_prime_UTR_variant	13/13	ENST00000356976.8	NP_036539.1	Q9NRD5-1A0A024R1J5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PICK1	ENST00000356976.8 linkuse as main transcript	c.*8G>A	3_prime_UTR_variant	13/13	1	NM_012407.4	ENSP00000349465.3	Q9NRD5-1
PICK1	ENST00000404072.7 linkuse as main transcript	c.*8G>A	3_prime_UTR_variant	13/13	2		ENSP00000385205.3	Q9NRD5-1
PICK1	ENST00000484021.5 linkuse as main transcript	n.1978G>A	non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes

AF:

0.000776

AC:

118

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0234

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00259

AC:

617

AN:

238230

Hom.:

AF XY:

0.00358

AC XY:

465

AN XY:

130034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.0198

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000668

Gnomad OTH exome

AF:

0.00137

GnomAD4 exome

AF:

0.00128

AC:

1867

AN:

1453578

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

1352

AN XY:

722158

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

Gnomad4 AMR exome

AF:

0.0000898

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0202

Gnomad4 FIN exome

AF:

0.0000587

Gnomad4 NFE exome

AF:

0.0000280

Gnomad4 OTH exome

AF:

0.00122

GnomAD4 genome

AF:

0.000762

AC:

116

AN:

152204

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000221

Hom.:

Bravo

AF:

0.000151

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PICK1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.7

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over