3-73624795-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015009.3(PDZRN3):​c.31G>T​(p.Asp11Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PDZRN3
NM_015009.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.70
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-AS1 (HGNC:40814): (PDZRN3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17791164).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDZRN3NM_015009.3 linkc.31G>T p.Asp11Tyr missense_variant Exon 1 of 10 ENST00000263666.9 NP_055824.1
PDZRN3XM_017005942.3 linkc.31G>T p.Asp11Tyr missense_variant Exon 1 of 9 XP_016861431.1
PDZRN3-AS1NR_046681.1 linkn.399-617C>A intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDZRN3ENST00000263666.9 linkc.31G>T p.Asp11Tyr missense_variant Exon 1 of 10 1 NM_015009.3 ENSP00000263666.4 Q9UPQ7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1245248
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
606796
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 30, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.31G>T (p.D11Y) alteration is located in exon 1 (coding exon 1) of the PDZRN3 gene. This alteration results from a G to T substitution at nucleotide position 31, causing the aspartic acid (D) at amino acid position 11 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Uncertain
25
DANN
Benign
0.97
DEOGEN2
Benign
0.029
T;.
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L;L
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.3
N;D
REVEL
Benign
0.053
Sift
Benign
0.036
D;D
Sift4G
Uncertain
0.038
D;D
Polyphen
0.0010
B;.
Vest4
0.37
MutPred
0.41
Loss of disorder (P = 0.0114);Loss of disorder (P = 0.0114);
MVP
0.18
MPC
1.9
ClinPred
0.57
D
GERP RS
3.1
Varity_R
0.24
gMVP
0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-73673946; API