3-73570410-G-C

Position:

• chr3-73570410-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+31944C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,198 control chromosomes in the GnomAD database, including 1,308 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 0.13 (1308 hom., cov: 33)
• Consequence: PDZRN3 NM_015009.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZRN3	NM_015009.3	c.918+31944C>G		intron_variant		ENST00000263666.9	NP_055824.1
PDZRN3	XM_017005942.3	c.831+31944C>G		intron_variant			XP_016861431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZRN3	ENST00000263666.9	c.918+31944C>G		intron_variant		1	NM_015009.3	ENSP00000263666	P1
PDZRN3	ENST00000308537.4	c.918+31944C>G		intron_variant		1		ENSP00000308831

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19220 AN: 152080 Hom.: 1306 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.126 AC: 19245 AN: 152198 Hom.: 1308 Cov.: 33 AF XY: 0.128 AC XY: 9501 AN XY: 74420

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.147

Alfa AF: 0.127 Hom.: 698

Bravo AF: 0.132

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.65

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: rs11128347; hg19: chr3-73619561;