rs285589

Positions:

• chr12-41550605-T-C

Variant summary

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

The NM_001164595.2(PDZRN4):​c.1204-2051T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,068 control chromosomes in the GnomAD database, including 5,120 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 0.23 (5120 hom., cov: 32)
• Consequence: PDZRN4 NM_001164595.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.529

Genes affected

PDZRN4 (HGNC:30552): (PDZ domain containing ring finger 4) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PDZRN4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZRN4	NM_001164595.2	c.1204-2051T>C		intron_variant		ENST00000402685.7	NP_001158067.1
PDZRN4	NM_013377.4	c.430-2051T>C		intron_variant			NP_037509.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZRN4	ENST00000402685.7	c.1204-2051T>C		intron_variant		2	NM_001164595.2	ENSP00000384197.2

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34776 AN: 151948 Hom.: 5118 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.227

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.229 AC: 34808 AN: 152068 Hom.: 5120 Cov.: 32 AF XY: 0.226 AC XY: 16819 AN XY: 74350

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.224

Alfa AF: 0.192 Hom.: 847

Bravo AF: 0.245

Asia WGS AF: 0.200 AC: 699 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.77

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: rs285589; hg19: chr12-41944407;