1-145686522-C-A

Variant names:

• chr1-145686522-C-A
• rs782407042
• NM_001201325.2:c.415G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001371361.1(PDZK1):​c.-70G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: PDZK1 NM_001371361.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.09
• Publications: 0 publications found

Genes affected

PDZK1 (HGNC:8821): (PDZ domain containing 1) This gene encodes a PDZ domain-containing scaffolding protein. PDZ domain-containing molecules bind to and mediate the subcellular localization of target proteins. The encoded protein mediates the localization of cell surface proteins and plays a critical role in cholesterol metabolism by regulating the HDL receptor, scavenger receptor class B type 1. Single nucleotide polymorphisms in this gene may be associated with metabolic syndrome, and overexpression of this gene may play a role in drug resistance of multiple myeloma. Pseudogenes of this gene are located on the long arm of chromosome 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37130657).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371361.1. 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
	PDZK1	NM_001201325.2	MANE Select	c.415G>T	p.Val139Leu	missense	Exon 3 of 9	NP_001188254.1	Q5T2W1-1
	PDZK1	NM_001371361.1		c.-70G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 8	NP_001358290.1
	PDZK1	NM_002614.4		c.415G>T	p.Val139Leu	missense	Exon 4 of 10	NP_002605.2	Q5T2W1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZK1	ENST00000417171.6	TSL:1 MANE Select	c.415G>T	p.Val139Leu	missense	Exon 3 of 9	ENSP00000394485.1	Q5T2W1-1
	PDZK1	ENST00000960532.1		c.415G>T	p.Val139Leu	missense	Exon 3 of 11	ENSP00000630591.1
	PDZK1	ENST00000907412.1		c.415G>T	p.Val139Leu	missense	Exon 4 of 12	ENSP00000577471.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_noAF	Benign	-0.10
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.37	T
PhyloP100		3.1
PROVEAN	Benign	-1.7	N
Sift	Benign	0.18	T
Sift4G	Benign	0.47	T
Vest4		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.84

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: rs782407042; hg19: chr1-145748542;