rs587603913

Variant names:

• chr1-145686641-C-T
• rs587603913
• NM_001201325.2:c.296G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001201325.2(PDZK1):​c.296G>A​(p.Arg99Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,595,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: PDZK1 NM_001201325.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0320
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047849506).
• BP6: Variant 1-145686641-C-T is Benign according to our data. Variant chr1-145686641-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3416805.Status of the report is criteria_provided_single_submitter, 1 stars.

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.296G>A	p.Arg99Gln	missense	Exon 3 of 9	NP_001188254.1	Q5T2W1-1
	PDZK1	NM_002614.4		c.296G>A	p.Arg99Gln	missense	Exon 4 of 10	NP_002605.2	Q5T2W1-1
	PDZK1	NM_001371359.1		c.296G>A	p.Arg99Gln	missense	Exon 3 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.296G>A	p.Arg99Gln	missense	Exon 3 of 9	ENSP00000394485.1	Q5T2W1-1
	PDZK1	ENST00000960532.1		c.296G>A	p.Arg99Gln	missense	Exon 3 of 11	ENSP00000630591.1
	PDZK1	ENST00000907412.1		c.296G>A	p.Arg99Gln	missense	Exon 4 of 12	ENSP00000577471.1

Frequencies

GnomAD3 genomes AF: 0.0000330 AC: 5 AN: 151664 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

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: 0.0000736

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000496 AC: 11 AN: 221776 AF XY: 0.0000665

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000647

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000716

Gnomad OTH exome AF: 0.000181

GnomAD4 exome AF: 0.0000333 AC: 48 AN: 1443480 Hom.: 0 Cov.: 27 AF XY: 0.0000488 AC XY: 35 AN XY: 717642

African (AFR) AF: 0.00 AC: 0 AN: 33070

American (AMR) AF: 0.0000463 AC: 2 AN: 43176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25894

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39410

South Asian (SAS) AF: 0.0000470 AC: 4 AN: 85024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53140

Middle Eastern (MID) AF: 0.000244 AC: 1 AN: 4104

European-Non Finnish (NFE) AF: 0.0000327 AC: 36 AN: 1099938

Other (OTH) AF: 0.0000670 AC: 4 AN: 59724

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151782 Hom.: 0 Cov.: 29 AF XY: 0.0000270 AC XY: 2 AN XY: 74150

African (AFR) AF: 0.00 AC: 0 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

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

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67926

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000340

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.060
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.32
DEOGEN2	Benign	0.094	T
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.048	T
PhyloP100		0.032
PROVEAN	Benign	-0.040	N
Sift	Benign	0.28	T
Sift4G	Benign	0.46	T
Vest4		0.095
gMVP		0.64

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: rs587603913; hg19: chr1-145748423;