chr1-145707383-A-G

Position:

• chr1-145707383-A-G

Variant summary

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

The NM_002614.4(PDZK1):​c.-140T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,462 control chromosomes in the GnomAD database, including 67,579 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 0.94 (67518 hom., cov: 34)
  • Exomes 𝑓: 0.94 (61 hom.)
• Consequence: PDZK1 NM_002614.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZK1	NM_001201325.2	c.-69T>C		upstream_gene_variant		ENST00000417171.6	NP_001188254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZK1	ENST00000451928.6	c.-69T>C		5_prime_UTR_variant	1/7	2		ENSP00000403422.2
PDZK1	ENST00000443667.1	c.-69T>C		5_prime_UTR_variant	2/6	5		ENSP00000409291.1
PDZK1	ENST00000417171.6	c.-69T>C		upstream_gene_variant		1	NM_001201325.2	ENSP00000394485.1

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143166 AN: 152208 Hom.: 67463 Cov.: 34

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.953

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.960

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.939

Gnomad OTH AF: 0.950

GnomAD4 exome AF: 0.941 AC: 128 AN: 136 Hom.: 61 Cov.: 0 AF XY: 0.957 AC XY: 88 AN XY: 92

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.934

Gnomad4 OTH exome AF: 0.875

GnomAD4 genome AF: 0.941 AC: 143280 AN: 152326 Hom.: 67518 Cov.: 34 AF XY: 0.939 AC XY: 69949 AN XY: 74476

Gnomad4 AFR AF: 0.963

Gnomad4 AMR AF: 0.952

Gnomad4 ASJ AF: 0.953

Gnomad4 EAS AF: 0.835

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.960

Gnomad4 NFE AF: 0.939

Gnomad4 OTH AF: 0.951

Alfa AF: 0.938 Hom.: 95440

Bravo AF: 0.945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1797052; hg19: chr1-145727683;