12-41327628-C-T

Position:

• chr12-41327628-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.843+133440C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 152,212 control chromosomes in the GnomAD database, including 63,236 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 0.91 (63236 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZRN4	NM_001164595.2	c.843+133440C>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.843+133440C>T		intron_variant		2	NM_001164595.2	ENSP00000384197	P1

Frequencies

GnomAD3 genomes AF: 0.907 AC: 137933 AN: 152096 Hom.: 63193 Cov.: 33

Gnomad AFR AF: 0.771

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.977

Gnomad OTH AF: 0.923

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

GnomAD4 genome AF: 0.907 AC: 138033 AN: 152212 Hom.: 63236 Cov.: 33 AF XY: 0.906 AC XY: 67388 AN XY: 74420

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.956

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.977

Gnomad4 OTH AF: 0.924

Alfa AF: 0.959 Hom.: 117056

Bravo AF: 0.901

Asia WGS AF: 0.838 AC: 2913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.55

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: rs1880887; hg19: chr12-41721430;