1-145682585-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001201325.2(PDZK1):c.512G>A(p.Arg171Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 1,578,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (0 hom., cov: 30)
  • Exomes 𝑓: 0.024 (0 hom.)
• Consequence: PDZK1 NM_001201325.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.982

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052711666).
• BP6: Variant 1-145682585-C-T is Benign according to our data. Variant chr1-145682585-C-T is described in ClinVar as [Benign]. Clinvar id is 769244.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZK1	NM_001201325.2	c.512G>A	p.Arg171Lys	missense_variant	4/9	ENST00000417171.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZK1	ENST00000417171.6	c.512G>A	p.Arg171Lys	missense_variant	4/9	1	NM_001201325.2	P1
PDZK1	ENST00000344770.6	c.512G>A	p.Arg171Lys	missense_variant	4/9	5		P1
PDZK1	ENST00000443667.1	c.512G>A	p.Arg171Lys	missense_variant	5/6	5
PDZK1	ENST00000451928.6	c.460+3892G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4588 AN: 148368 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.00989

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.00991

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0243 AC: 34750 AN: 1430028 Hom.: 0 Cov.: 32 AF XY: 0.0238 AC XY: 16953 AN XY: 712098

Gnomad4 AFR exome AF: 0.0576

Gnomad4 AMR exome AF: 0.0157

Gnomad4 ASJ exome AF: 0.0117

Gnomad4 EAS exome AF: 0.0346

Gnomad4 SAS exome AF: 0.00755

Gnomad4 FIN exome AF: 0.0188

Gnomad4 NFE exome AF: 0.0252

Gnomad4 OTH exome AF: 0.0257

GnomAD4 genome AF: 0.0311 AC: 4610 AN: 148458 Hom.: 0 Cov.: 30 AF XY: 0.0307 AC XY: 2229 AN XY: 72600

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.0236

Gnomad4 ASJ AF: 0.00989

Gnomad4 EAS AF: 0.0328

Gnomad4 SAS AF: 0.00970

Gnomad4 FIN AF: 0.0175

Gnomad4 NFE AF: 0.0265

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0339 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_noAF	Uncertain	0.080
Cadd	Benign	10
Dann	Benign	0.30
DEOGEN2	Benign	0.067	T;T;.
LIST_S2	Benign	0.091	T;.;T
MetaRNN	Benign	0.0053	T;T;T
PROVEAN	Benign	-0.41	N;N;N
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;.
Vest4		0.084
gMVP		0.47

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: rs138296787; hg19: chr1-145752479; COSMIC: COSV61092011;