Genetic Variant PDZRN3:p.Ala183Thr (chr3-73624279-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015009.3(PDZRN3):c.547G>A(p.Ala183Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000808 in 1,236,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A183S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.1e-7 ( 0 hom. )

Consequence

PDZRN3
NM_015009.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.46

Publications

0 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:

PDZRN3-AS1 (HGNC:40814): (PDZRN3 antisense RNA 1)

PDZRN3-AS1 links:

ENSG00000278934 (HGNC:):

ENSG00000278934 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12059957).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015009.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZRN3	NM_015009.3	MANE Select	c.547G>A	p.Ala183Thr	missense	Exon 1 of 10	NP_055824.1	Q9UPQ7-1
	PDZRN3-AS1	NR_046681.1		n.398+314C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDZRN3	ENST00000263666.9	TSL:1 MANE Select	c.547G>A	p.Ala183Thr	missense	Exon 1 of 10	ENSP00000263666.4	Q9UPQ7-1
PDZRN3	ENST00000308537.4	TSL:1	c.547G>A	p.Ala183Thr	missense	Exon 1 of 4	ENSP00000308831.4	Q9UPQ7-2
PDZRN3-AS1	ENST00000478988.3	TSL:5	n.380+314C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.08e-7

AC:

AN:

1236948

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

601124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24312

American (AMR)

AF:

0.00

AC:

AN:

12578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18102

East Asian (EAS)

AF:

0.00

AC:

AN:

28002

South Asian (SAS)

AF:

0.00

AC:

AN:

57160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3764

European-Non Finnish (NFE)

AF:

9.88e-7

AC:

AN:

1011784

Other (OTH)

AF:

0.00

AC:

AN:

50914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Benign

-0.17

Eigen_PC

Benign

0.018

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

3.5

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.20

REVEL

Benign

0.042

Sift

Benign

0.17

Sift4G

Benign

0.075

Polyphen

0.18

Vest4

0.11

MutPred

0.25

Gain of phosphorylation at A183 (P = 0.0805)

MVP

0.24

MPC

1.4

ClinPred

0.37

GERP RS

5.0

Varity_R

0.14

gMVP

0.21

Mutation Taster

=76/24

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over