12-41504058-T-C

Variant names:

• chr12-41504058-T-C
• rs2733285
• NM_001164595.2:c.844-2398T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164595.2(PDZRN4):​c.844-2398T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 151,768 control chromosomes in the GnomAD database, including 23,063 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 0.54 (23063 hom., cov: 31)
• Consequence: PDZRN4 NM_001164595.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164595.2. 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
	PDZRN4	NM_001164595.2	MANE Select	c.844-2398T>C		intron	N/A	NP_001158067.1	Q6ZMN7-1
	PDZRN4	NM_013377.4		c.70-2398T>C		intron	N/A	NP_037509.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZRN4	ENST00000402685.7	TSL:2 MANE Select	c.844-2398T>C		intron	N/A	ENSP00000384197.2	Q6ZMN7-1
	PDZRN4	ENST00000539469.6	TSL:1	c.70-2398T>C		intron	N/A	ENSP00000439990.2	Q6ZMN7-2
	PDZRN4	ENST00000298919.7	TSL:2	c.64-2398T>C		intron	N/A	ENSP00000298919.7	Q6ZMN7-4

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82197 AN: 151650 Hom.: 23023 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.542 AC: 82275 AN: 151768 Hom.: 23063 Cov.: 31 AF XY: 0.539 AC XY: 40000 AN XY: 74146

African (AFR) AF: 0.699 AC: 28942 AN: 41396

American (AMR) AF: 0.469 AC: 7158 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1594 AN: 3464

East Asian (EAS) AF: 0.487 AC: 2488 AN: 5106

South Asian (SAS) AF: 0.544 AC: 2609 AN: 4800

European-Finnish (FIN) AF: 0.474 AC: 4992 AN: 10524

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32940 AN: 67902

Other (OTH) AF: 0.529 AC: 1117 AN: 2112

Alfa AF: 0.531 Hom.: 2865

Bravo AF: 0.545

Asia WGS AF: 0.494 AC: 1722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2733285; hg19: chr12-41897860;