1-145704906-C-T

Position:

• chr1-145704906-C-T

Variant summary

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

The NM_001201325.2(PDZK1):​c.-3+2411G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,912 control chromosomes in the GnomAD database, including 15,251 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 0.44 (15251 hom., cov: 32)
• Consequence: PDZK1 NM_001201325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.25

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]

PDZK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZK1	NM_001201325.2	c.-3+2411G>A		intron_variant		ENST00000417171.6	NP_001188254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZK1	ENST00000417171.6	c.-3+2411G>A		intron_variant		1	NM_001201325.2	ENSP00000394485.1
PDZK1	ENST00000451928.6	c.-3+2411G>A		intron_variant		2		ENSP00000403422.2
PDZK1	ENST00000443667.1	c.-3+2411G>A		intron_variant		5		ENSP00000409291.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66693 AN: 151796 Hom.: 15236 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.439 AC: 66753 AN: 151912 Hom.: 15251 Cov.: 32 AF XY: 0.441 AC XY: 32705 AN XY: 74242

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.370

Gnomad4 OTH AF: 0.463

Alfa AF: 0.396 Hom.: 27742

Bravo AF: 0.455

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.055

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: rs1298954; hg19: chr1-145730160;