1-145687960-C-T

Position:

• chr1-145687960-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001201325.2(PDZK1):​c.62G>A​(p.Gly21Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PDZK1 NM_001201325.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.01

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZK1	NM_001201325.2	c.62G>A	p.Gly21Asp	missense_variant	2/9	ENST00000417171.6	NP_001188254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZK1	ENST00000417171.6	c.62G>A	p.Gly21Asp	missense_variant	2/9	1	NM_001201325.2	ENSP00000394485	P1
PDZK1	ENST00000344770.6	c.62G>A	p.Gly21Asp	missense_variant	2/9	5		ENSP00000342143	P1
PDZK1	ENST00000451928.6	c.62G>A	p.Gly21Asp	missense_variant	2/7	2		ENSP00000403422
PDZK1	ENST00000443667.1	c.62G>A	p.Gly21Asp	missense_variant	3/6	5		ENSP00000409291

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Martin Pollak Laboratory, Beth Israel Deaconess Medical Center

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_noAF	Pathogenic	0.35
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	.;T;T;.
LIST_S2	Uncertain	0.87	D;D;.;D
MetaRNN	Pathogenic	0.84	D;D;D;D
PROVEAN	Pathogenic	-5.9	D;D;D;D
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.043	D;D;D;.
Vest4		0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs387907448; hg19: chr1-145747105;