rs11576685

Positions:

• chr1-145691969-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001201325.2(PDZK1):​c.-2-3946A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 150,498 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.025 (77 hom., cov: 32)
• Consequence: PDZK1 NM_001201325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0251 (3775/150498) while in subpopulation NFE AF= 0.0372 (2514/67494). AF 95% confidence interval is 0.036. There are 77 homozygotes in gnomad4. There are 1842 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 77 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZK1	NM_001201325.2	c.-2-3946A>G		intron_variant		ENST00000417171.6	NP_001188254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZK1	ENST00000417171.6	c.-2-3946A>G		intron_variant		1	NM_001201325.2	ENSP00000394485	P1
PDZK1	ENST00000443667.1	c.-2-3946A>G		intron_variant		5		ENSP00000409291
PDZK1	ENST00000451928.6	c.-2-3946A>G		intron_variant		2		ENSP00000403422

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3778 AN: 150388 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.00636

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.0357

Gnomad MID AF: 0.0422

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0327

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0251 AC: 3775 AN: 150498 Hom.: 77 Cov.: 32 AF XY: 0.0251 AC XY: 1842 AN XY: 73472

Gnomad4 AFR AF: 0.00634

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0102

Gnomad4 FIN AF: 0.0357

Gnomad4 NFE AF: 0.0372

Gnomad4 OTH AF: 0.0323

Alfa AF: 0.0366 Hom.: 136

Bravo AF: 0.0242

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs11576685; hg19: chr1-145743096;