Variant 1-145682585-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000417171.6(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
ENST00000417171.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.982

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
PDZK1	NM_001201325.2 linkuse as main transcript	c.512G>A	p.Arg171Lys	missense_variant	4/9	ENST00000417171.6	NP_001188254.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZK1	ENST00000417171.6 linkuse as main transcript	c.512G>A	p.Arg171Lys	missense_variant	4/9	1	NM_001201325.2	ENSP00000394485	P1	Q5T2W1-1
PDZK1	ENST00000344770.6 linkuse as main transcript	c.512G>A	p.Arg171Lys	missense_variant	4/9	5		ENSP00000342143	P1	Q5T2W1-1
PDZK1	ENST00000443667.1 linkuse as main transcript	c.512G>A	p.Arg171Lys	missense_variant	5/6	5		ENSP00000409291
PDZK1	ENST00000451928.6 linkuse as main transcript	c.460+3892G>A		intron_variant		2		ENSP00000403422		Q5T2W1-2

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4588

AN:

148368

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0238

AC XY:

16953

AN XY:

712098

show subpopulations

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.:

Cov.:

AF XY:

0.0307

AC XY:

2229

AN XY:

72600

show subpopulations

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.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over