Genetic Variant PDZRN3:c.*686T>C (chr3-73382679-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000263666.9(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
ENST00000263666.9 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.882

Publications

12 publications found

Variant links:

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 links:

ENSG00000309320 (HGNC:):

ENSG00000309320 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263666.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PDZRN3	NM_015009.3	MANE Select	c.*686T>C	3_prime_UTR	Exon 10 of 10	NP_055824.1
PDZRN3	NM_001303141.2		c.*686T>C	3_prime_UTR	Exon 8 of 8	NP_001290070.1
PDZRN3	NM_001303142.2		c.*686T>C	3_prime_UTR	Exon 8 of 8	NP_001290071.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PDZRN3	ENST00000263666.9	TSL:1 MANE Select	c.*686T>C	3_prime_UTR	Exon 10 of 10	ENSP00000263666.4
PDZRN3	ENST00000494559.5	TSL:5	c.*686T>C	3_prime_UTR	Exon 7 of 7	ENSP00000419095.1
ENSG00000309320	ENST00000840257.1		n.80-51008A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

79046

AN:

151936

Hom.:

20745

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.553

AC XY:

146

AN XY:

264

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.570

AC:

243

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.520

AC:

79099

AN:

152054

Hom.:

20762

Cov.:

AF XY:

0.526

AC XY:

39058

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.527

AC:

21833

AN:

41450

American (AMR)

AF:

0.562

AC:

8590

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

1785

AN:

3470

East Asian (EAS)

AF:

0.709

AC:

3665

AN:

5172

South Asian (SAS)

AF:

0.447

AC:

2155

AN:

4816

European-Finnish (FIN)

AF:

0.600

AC:

6350

AN:

10580

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.484

AC:

32925

AN:

67966

Other (OTH)

AF:

0.536

AC:

1131

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1993

3986

5980

7973

9966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

690

1380

2070

2760

3450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.499

Hom.:

33323

Bravo

AF:

0.524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.3

(source)

DANN

Benign

0.83

PhyloP100

0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over