NM_001201325.2:c.1260G>C

Variant names:

• chr1-145672976-C-G
• NM_001201325.2:c.1260G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001201325.2(PDZK1):​c.1260G>C​(p.Glu420Asp) variant causes a missense 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. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 28)
• Consequence: PDZK1 NM_001201325.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.19
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0954971).

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.1260G>C	p.Glu420Asp	missense	Exon 8 of 9	NP_001188254.1	Q5T2W1-1
	PDZK1	NM_002614.4		c.1260G>C	p.Glu420Asp	missense	Exon 9 of 10	NP_002605.2	Q5T2W1-1
	PDZK1	NM_001371359.1		c.1260G>C	p.Glu420Asp	missense	Exon 8 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.1260G>C	p.Glu420Asp	missense	Exon 8 of 9	ENSP00000394485.1	Q5T2W1-1
	PDZK1	ENST00000960532.1		c.1392G>C	p.Glu464Asp	missense	Exon 10 of 11	ENSP00000630591.1
	PDZK1	ENST00000907412.1		c.1341G>C	p.Glu447Asp	missense	Exon 11 of 12	ENSP00000577471.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 28

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	Benign	0.096
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.71
DANN	Benign	0.78
DEOGEN2	Benign	0.056	T
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.095	T
PhyloP100		-1.2
PROVEAN	Benign	0.31	N
Sift	Benign	0.45	T
Sift4G	Benign	0.67	T
Vest4		0.21
gMVP		0.49

Splicing

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

Other links and lift over

hg19: chr1-145762083;