12-41353626-C-T

Position:

• chr12-41353626-C-T

Variant summary

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

The NM_001164595.2(PDZRN4):​c.844-152830C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 151,960 control chromosomes in the GnomAD database, including 60,748 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 0.89 (60748 hom., cov: 30)
• Consequence: PDZRN4 NM_001164595.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZRN4	NM_001164595.2	c.844-152830C>T		intron_variant		ENST00000402685.7	NP_001158067.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZRN4	ENST00000402685.7	c.844-152830C>T		intron_variant		2	NM_001164595.2	ENSP00000384197.2

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135493 AN: 151842 Hom.: 60701 Cov.: 30

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.892 AC: 135595 AN: 151960 Hom.: 60748 Cov.: 30 AF XY: 0.893 AC XY: 66332 AN XY: 74260

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.952

Gnomad4 NFE AF: 0.930

Gnomad4 OTH AF: 0.900

Alfa AF: 0.920 Hom.: 132574

Bravo AF: 0.889

Asia WGS AF: 0.850 AC: 2954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.033
DANN	Benign	0.26

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: rs10785246; hg19: chr12-41747428;