rs6794128

Positions:

• chr3-73513983-G-A
• chr3-73513983-G-C

Variant summary

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

The NM_015009.3(PDZRN3):​c.918+88371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,060 control chromosomes in the GnomAD database, including 19,497 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 0.50 (19497 hom., cov: 33)
• Consequence: PDZRN3 NM_015009.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

Genes affected

PDZRN3 (HGNC:17704): (PDZ domain containing ring finger 3) This gene encodes a member of the LNX (Ligand of Numb Protein-X) family of RING-type ubiquitin E3 ligases. This protein may function in vascular morphogenesis and the differentiation of adipocytes, osteoblasts and myoblasts. This protein may be targeted for degradation by the human papilloma virus E6 protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

PDZRN3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZRN3	NM_015009.3	c.918+88371C>T		intron_variant		ENST00000263666.9	NP_055824.1
PDZRN3	NM_001303139.2	c.12+55168C>T		intron_variant			NP_001290068.1
PDZRN3	NM_001303140.2	c.-112+47468C>T		intron_variant			NP_001290069.1
PDZRN3	XM_017005942.3	c.831+88371C>T		intron_variant			XP_016861431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZRN3	ENST00000263666.9	c.918+88371C>T		intron_variant		1	NM_015009.3	ENSP00000263666.4

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76467 AN: 151942 Hom.: 19478 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.503 AC: 76522 AN: 152060 Hom.: 19497 Cov.: 33 AF XY: 0.508 AC XY: 37765 AN XY: 74320

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.524

Alfa AF: 0.503 Hom.: 7673

Bravo AF: 0.506

Asia WGS AF: 0.501 AC: 1743 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.5
DANN	Benign	0.67

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: rs6794128; hg19: chr3-73563134;