rs1284300

Positions:

• chr1-145687602-G-A
• chr1-145687602-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001201325.2(PDZK1):​c.210+210C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 150,848 control chromosomes in the GnomAD database, including 686 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 0.083 (686 hom., cov: 31)
• Consequence: PDZK1 NM_001201325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZK1	NM_001201325.2	c.210+210C>T		intron_variant		ENST00000417171.6	NP_001188254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZK1	ENST00000417171.6	c.210+210C>T		intron_variant		1	NM_001201325.2	ENSP00000394485	P1
PDZK1	ENST00000344770.6	c.210+210C>T		intron_variant		5		ENSP00000342143	P1
PDZK1	ENST00000443667.1	c.210+210C>T		intron_variant		5		ENSP00000409291
PDZK1	ENST00000451928.6	c.210+210C>T		intron_variant		2		ENSP00000403422

Frequencies

GnomAD3 genomes AF: 0.0826 AC: 12457 AN: 150748 Hom.: 684 Cov.: 31

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.0385

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.0721

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

GnomAD4 genome AF: 0.0826 AC: 12460 AN: 150848 Hom.: 686 Cov.: 31 AF XY: 0.0859 AC XY: 6318 AN XY: 73586

Gnomad4 AFR AF: 0.0453

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.0606

Gnomad4 NFE AF: 0.0810

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0778 Hom.: 758

Bravo AF: 0.0825

Asia WGS AF: 0.180 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1284300; hg19: chr1-145747463;