rs12814017

Positions:

• chr12-41564298-A-G
• chr12-41564298-A-T

Variant summary

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

The NM_001164595.2(PDZRN4):​c.1467+649A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,216 control chromosomes in the GnomAD database, including 2,022 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 0.15 (2022 hom., cov: 33)
• Consequence: PDZRN4 NM_001164595.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408

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]

LOC107984498 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZRN4	NM_001164595.2	c.1467+649A>G		intron_variant		ENST00000402685.7	NP_001158067.1
LOC107984498	XR_001749090.2	n.476+1533T>C		intron_variant, non_coding_transcript_variant
PDZRN4	NM_013377.4	c.693+649A>G		intron_variant			NP_037509.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZRN4	ENST00000402685.7	c.1467+649A>G		intron_variant		2	NM_001164595.2	ENSP00000384197	P1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22814 AN: 152098 Hom.: 2026 Cov.: 33

Gnomad AFR AF: 0.0728

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.150 AC: 22814 AN: 152216 Hom.: 2022 Cov.: 33 AF XY: 0.146 AC XY: 10895 AN XY: 74422

Gnomad4 AFR AF: 0.0727

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.0283

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.151

Alfa AF: 0.197 Hom.: 3855

Bravo AF: 0.145

Asia WGS AF: 0.0750 AC: 263 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.64

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: rs12814017; hg19: chr12-41958100;