chr1-145673668-A-C

Variant names:

• chr1-145673668-A-C
• rs1481611812
• NM_001201325.2:c.1204T>G

Variant summary

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

The NM_001201325.2(PDZK1):​c.1204T>G​(p.Phe402Val) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000048 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0000035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDZK1 NM_001201325.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.21
• 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.

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.1204T>G	p.Phe402Val	missense	Exon 7 of 9	NP_001188254.1	Q5T2W1-1
	PDZK1	NM_002614.4		c.1204T>G	p.Phe402Val	missense	Exon 8 of 10	NP_002605.2	Q5T2W1-1
	PDZK1	NM_001371359.1		c.1204T>G	p.Phe402Val	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.1204T>G	p.Phe402Val	missense	Exon 7 of 9	ENSP00000394485.1	Q5T2W1-1
	PDZK1	ENST00000960532.1		c.1336T>G	p.Phe446Val	missense	Exon 9 of 11	ENSP00000630591.1
	PDZK1	ENST00000907412.1		c.1285T>G	p.Phe429Val	missense	Exon 10 of 12	ENSP00000577471.1

Frequencies

GnomAD3 genomes AF: 0.0000479 AC: 7 AN: 146160 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000345 AC: 5 AN: 1447968 Hom.: 0 Cov.: 27 AF XY: 0.00000416 AC XY: 3 AN XY: 720802

African (AFR) AF: 0.000151 AC: 5 AN: 33174

American (AMR) AF: 0.00 AC: 0 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25926

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 85308

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102324

Other (OTH) AF: 0.00 AC: 0 AN: 59790

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000479 AC: 7 AN: 146160 Hom.: 0 Cov.: 24 AF XY: 0.0000707 AC XY: 5 AN XY: 70672

African (AFR) AF: 0.000177 AC: 7 AN: 39500

American (AMR) AF: 0.00 AC: 0 AN: 14438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.00 AC: 0 AN: 4948

South Asian (SAS) AF: 0.00 AC: 0 AN: 4452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66260

Other (OTH) AF: 0.00 AC: 0 AN: 1988

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000529

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	0.21
BayesDel_noAF	Pathogenic	0.43
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
LIST_S2	Benign	0.84	T
MetaRNN	Uncertain	0.74	D
PhyloP100		6.2
PROVEAN	Uncertain	-4.3	D
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.016	D
Vest4		0.66
gMVP		0.81

Splicing

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

Other links and lift over

dbSNP: rs1481611812; hg19: chr1-145761391;