chr1-145673685-C-T

Variant names:

• chr1-145673685-C-T
• rs587733119
• NM_001201325.2:c.1187G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001201325.2(PDZK1):​c.1187G>A​(p.Arg396Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R396W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDZK1 NM_001201325.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.124
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04596281).
• BP6: Variant 1-145673685-C-T is Benign according to our data. Variant chr1-145673685-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3416803.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201325.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZK1	NM_001201325.2	MANE Select	c.1187G>A	p.Arg396Gln	missense	Exon 7 of 9	NP_001188254.1	Q5T2W1-1
	PDZK1	NM_002614.4		c.1187G>A	p.Arg396Gln	missense	Exon 8 of 10	NP_002605.2	Q5T2W1-1
	PDZK1	NM_001371359.1		c.1187G>A	p.Arg396Gln	missense	Exon 7 of 10	NP_001358288.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZK1	ENST00000417171.6	TSL:1 MANE Select	c.1187G>A	p.Arg396Gln	missense	Exon 7 of 9	ENSP00000394485.1	Q5T2W1-1
	PDZK1	ENST00000960532.1		c.1319G>A	p.Arg440Gln	missense	Exon 9 of 11	ENSP00000630591.1
	PDZK1	ENST00000907412.1		c.1268G>A	p.Arg423Gln	missense	Exon 10 of 12	ENSP00000577471.1

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 16 AN: 148552 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000298

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000747 AC: 6 AN: 80348 AF XY: 0.0000513

Gnomad AFR exome AF: 0.000775

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000307

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000241 AC: 35 AN: 1454596 Hom.: 0 Cov.: 30 AF XY: 0.0000249 AC XY: 18 AN XY: 723766

African (AFR) AF: 0.000420 AC: 14 AN: 33314

American (AMR) AF: 0.00 AC: 0 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.0000467 AC: 4 AN: 85622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4118

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1108016

Other (OTH) AF: 0.0000333 AC: 2 AN: 60010

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000108 AC: 16 AN: 148666 Hom.: 0 Cov.: 24 AF XY: 0.0000831 AC XY: 6 AN XY: 72244

African (AFR) AF: 0.000348 AC: 14 AN: 40272

American (AMR) AF: 0.00 AC: 0 AN: 14732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3428

East Asian (EAS) AF: 0.00 AC: 0 AN: 5044

South Asian (SAS) AF: 0.00 AC: 0 AN: 4578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000298 AC: 2 AN: 67204

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000106

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_noAF	Benign	-0.32
CADD	Benign	8.9
DANN	Benign	0.82
DEOGEN2	Benign	0.053	T
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.046	T
PhyloP100		-0.12
PROVEAN	Benign	-0.10	N
Sift	Benign	0.35	T
Sift4G	Benign	0.28	T
Vest4		0.078
gMVP		0.27

Splicing

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

Other links and lift over

dbSNP: rs587733119; hg19: chr1-145761374;