1-145682530-C-T

Variant names:

• chr1-145682530-C-T
• NM_001201325.2:c.567G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001201325.2(PDZK1):​c.567G>A​(p.Glu189Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PDZK1 NM_001201325.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.614
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 1-145682530-C-T is Benign according to our data. Variant chr1-145682530-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2639114.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.614 with no splicing effect.

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.567G>A	p.Glu189Glu	synonymous	Exon 4 of 9	NP_001188254.1	Q5T2W1-1
	PDZK1	NM_002614.4		c.567G>A	p.Glu189Glu	synonymous	Exon 5 of 10	NP_002605.2	Q5T2W1-1
	PDZK1	NM_001371359.1		c.567G>A	p.Glu189Glu	synonymous	Exon 4 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.567G>A	p.Glu189Glu	synonymous	Exon 4 of 9	ENSP00000394485.1	Q5T2W1-1
	PDZK1	ENST00000960532.1		c.567G>A	p.Glu189Glu	synonymous	Exon 4 of 11	ENSP00000630591.1
	PDZK1	ENST00000907412.1		c.567G>A	p.Glu189Glu	synonymous	Exon 5 of 12	ENSP00000577471.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456346 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 724650

African (AFR) AF: 0.00 AC: 0 AN: 33364

American (AMR) AF: 0.00 AC: 0 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4130

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108820

Other (OTH) AF: 0.0000166 AC: 1 AN: 60084

GnomAD4 genome Cov.: 29

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	2.9
DANN	Benign	0.31
PhyloP100		0.61
Mutation Taster		=1/199	disease causing (fs/PTC)

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

hg19: chr1-145752534;