22-38075083-GA-TT

Variant names:

• chr22-38075083-GA-TT
• NM_012407.4:c.1199_1200delGAinsTT
• PICK1 p.Arg400Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_012407.4(PICK1):​c.1199_1200delGAinsTT​(p.Arg400Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R400Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PICK1 NM_012407.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICK1	NM_012407.4	MANE Select	c.1199_1200delGAinsTT	p.Arg400Leu	missense	N/A	NP_036539.1	Q9NRD5-1
	PICK1	NM_001039583.1		c.1199_1200delGAinsTT	p.Arg400Leu	missense	N/A	NP_001034672.1	Q9NRD5-1
	PICK1	NM_001039584.1		c.1199_1200delGAinsTT	p.Arg400Leu	missense	N/A	NP_001034673.1	Q9NRD5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICK1	ENST00000356976.8	TSL:1 MANE Select	c.1199_1200delGAinsTT	p.Arg400Leu	missense	N/A	ENSP00000349465.3	Q9NRD5-1
	PICK1	ENST00000951428.1		c.1304_1305delGAinsTT	p.Arg435Leu	missense	N/A	ENSP00000621487.1
	PICK1	ENST00000951430.1		c.1304_1305delGAinsTT	p.Arg435Leu	missense	N/A	ENSP00000621489.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.29

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-38471090;