NM_001201325.2:c.1159G>C

Variant names:

• chr1-145673713-C-G
• rs1653329042
• NM_001201325.2:c.1159G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001201325.2(PDZK1):​c.1159G>C​(p.Gly387Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: PDZK1 NM_001201325.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201325.2. 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.1159G>C	p.Gly387Arg	missense	Exon 7 of 9	NP_001188254.1	Q5T2W1-1
	PDZK1	NM_002614.4		c.1159G>C	p.Gly387Arg	missense	Exon 8 of 10	NP_002605.2	Q5T2W1-1
	PDZK1	NM_001371359.1		c.1159G>C	p.Gly387Arg	missense	Exon 7 of 10	NP_001358288.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZK1	ENST00000417171.6	TSL:1 MANE Select	c.1159G>C	p.Gly387Arg	missense	Exon 7 of 9	ENSP00000394485.1	Q5T2W1-1
	PDZK1	ENST00000960532.1		c.1291G>C	p.Gly431Arg	missense	Exon 9 of 11	ENSP00000630591.1
	PDZK1	ENST00000907412.1		c.1240G>C	p.Gly414Arg	missense	Exon 10 of 12	ENSP00000577471.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151286 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000132 AC: 2 AN: 151406 Hom.: 0 Cov.: 24 AF XY: 0.0000135 AC XY: 1 AN XY: 73928

African (AFR) AF: 0.00 AC: 0 AN: 41200

American (AMR) AF: 0.00 AC: 0 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67896

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_noAF	Pathogenic	0.37
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.35	T
LIST_S2	Uncertain	0.90	D
MetaRNN	Uncertain	0.63	D
PhyloP100		4.0
PROVEAN	Pathogenic	-6.7	D
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Vest4		0.59
gMVP		0.88

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: rs1653329042; hg19: chr1-145761346;