rs713729

Variant names:

• chr22-38059462-T-A
• rs713729
• NM_012407.4:c.153+117T>A

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+117T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 759,668 control chromosomes in the GnomAD database, including 24,602 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 0.20 (4036 hom., cov: 32)
  • Exomes 𝑓: 0.25 (20566 hom.)
• Consequence: PICK1 NM_012407.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 15 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PICK1	NM_012407.4	c.153+117T>A		intron_variant	Intron 3 of 12	ENST00000356976.8	NP_036539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PICK1	ENST00000356976.8	c.153+117T>A		intron_variant	Intron 3 of 12	1	NM_012407.4	ENSP00000349465.3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30997 AN: 152098 Hom.: 4033 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.252 AC: 153297 AN: 607452 Hom.: 20566 AF XY: 0.249 AC XY: 79937 AN XY: 320392

African (AFR) AF: 0.0518 AC: 859 AN: 16570

American (AMR) AF: 0.165 AC: 5569 AN: 33808

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 4766 AN: 19396

East Asian (EAS) AF: 0.176 AC: 5608 AN: 31806

South Asian (SAS) AF: 0.176 AC: 10796 AN: 61466

European-Finnish (FIN) AF: 0.329 AC: 15660 AN: 47644

Middle Eastern (MID) AF: 0.209 AC: 841 AN: 4018

European-Non Finnish (NFE) AF: 0.282 AC: 101746 AN: 361166

Other (OTH) AF: 0.236 AC: 7452 AN: 31578

GnomAD4 genome AF: 0.204 AC: 31002 AN: 152216 Hom.: 4036 Cov.: 32 AF XY: 0.204 AC XY: 15222 AN XY: 74444

African (AFR) AF: 0.0544 AC: 2260 AN: 41556

American (AMR) AF: 0.187 AC: 2853 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 831 AN: 3472

East Asian (EAS) AF: 0.188 AC: 973 AN: 5186

South Asian (SAS) AF: 0.169 AC: 814 AN: 4828

European-Finnish (FIN) AF: 0.340 AC: 3605 AN: 10590

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19102 AN: 67980

Other (OTH) AF: 0.204 AC: 431 AN: 2112

Alfa AF: 0.242 Hom.: 640

Bravo AF: 0.187

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.80
PhyloP100		0.29
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: rs713729; hg19: chr22-38455469; COSMIC: COSV107447921; COSMIC: COSV107447921;