chr1-145687602-G-A

Variant names:

• chr1-145687602-G-A
• rs1284300
• NM_001201325.2:c.210+210C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
PDZK1	NM_001201325.2	c.210+210C>T		intron_variant	Intron 2 of 8	ENST00000417171.6	NP_001188254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZK1	ENST00000417171.6	c.210+210C>T		intron_variant	Intron 2 of 8	1	NM_001201325.2	ENSP00000394485.1
PDZK1	ENST00000344770.6	c.210+210C>T		intron_variant	Intron 2 of 8	5		ENSP00000342143.2
PDZK1	ENST00000451928.6	c.210+210C>T		intron_variant	Intron 2 of 6	2		ENSP00000403422.2
PDZK1	ENST00000443667.1	c.210+210C>T		intron_variant	Intron 3 of 5	5		ENSP00000409291.1

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

African (AFR) AF: 0.0453 AC: 1858 AN: 41042

American (AMR) AF: 0.144 AC: 2175 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3468

East Asian (EAS) AF: 0.181 AC: 924 AN: 5106

South Asian (SAS) AF: 0.216 AC: 1034 AN: 4792

European-Finnish (FIN) AF: 0.0606 AC: 618 AN: 10192

Middle Eastern (MID) AF: 0.0414 AC: 12 AN: 290

European-Non Finnish (NFE) AF: 0.0810 AC: 5495 AN: 67840

Other (OTH) AF: 0.0714 AC: 149 AN: 2086

Alfa AF: 0.0788 Hom.: 1478

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
PhyloP100		-0.037

Splicing

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

Other links and lift over

dbSNP: rs1284300; hg19: chr1-145747463;