3-73382679-A-G

Position:

• chr3-73382679-A-G

Variant summary

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

The NM_015009.3(PDZRN3):​c.*686T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,490 control chromosomes in the GnomAD database, including 20,830 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 0.52 (20762 hom., cov: 33)
  • Exomes 𝑓: 0.57 (68 hom.)
• Consequence: PDZRN3 NM_015009.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882

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]

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 = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZRN3	NM_015009.3	c.*686T>C		3_prime_UTR_variant	10/10	ENST00000263666.9	NP_055824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZRN3	ENST00000263666.9	c.*686T>C		3_prime_UTR_variant	10/10	1	NM_015009.3	ENSP00000263666	P1
PDZRN3	ENST00000494559.5	c.*686T>C		3_prime_UTR_variant	7/7	5		ENSP00000419095

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79046 AN: 151936 Hom.: 20745 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.539

GnomAD4 exome AF: 0.569 AC: 248 AN: 436 Hom.: 68 Cov.: 0 AF XY: 0.553 AC XY: 146 AN XY: 264

Gnomad4 FIN exome AF: 0.570

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.520 AC: 79099 AN: 152054 Hom.: 20762 Cov.: 33 AF XY: 0.526 AC XY: 39058 AN XY: 74306

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.536

Alfa AF: 0.498 Hom.: 26262

Bravo AF: 0.524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.3
DANN	Benign	0.83

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: rs7064; hg19: chr3-73431830; COSMIC: COSV55220244; COSMIC: COSV55220244;