rs748809996
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP5_ModerateBP4BS2
The NM_015009.3(PDZRN3):c.820G>A(p.Asp274Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,535,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.0000090 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
PDZRN3
NM_015009.3 missense
NM_015009.3 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 6.78
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP5
?
Variant 3-73602452-C-T is Pathogenic according to our data. Variant chr3-73602452-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 208395.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-73602452-C-T is described in Lovd as [Likely_pathogenic].
BP4
?
Computational evidence support a benign effect (MetaRNN=0.41003704). . Strength limited to SUPPORTING due to the PP5.
BS2
?
High AC in GnomAdExome4 at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDZRN3 | NM_015009.3 | c.820G>A | p.Asp274Asn | missense_variant | 3/10 | ENST00000263666.9 | |
PDZRN3 | XM_017005942.3 | c.733G>A | p.Asp245Asn | missense_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDZRN3 | ENST00000263666.9 | c.820G>A | p.Asp274Asn | missense_variant | 3/10 | 1 | NM_015009.3 | P1 | |
PDZRN3 | ENST00000308537.4 | c.820G>A | p.Asp274Asn | missense_variant | 3/4 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000904 AC: 1AN: 110594Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000223 AC: 5AN: 224408Hom.: 0 AF XY: 0.0000246 AC XY: 3AN XY: 121754
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GnomAD4 exome AF: 0.0000147 AC: 21AN: 1424538Hom.: 0 Cov.: 27 AF XY: 0.0000155 AC XY: 11AN XY: 710410
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GnomAD4 genome ? AF: 0.00000904 AC: 1AN: 110594Hom.: 0 Cov.: 33 AF XY: 0.0000190 AC XY: 1AN XY: 52656
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Childhood-onset schizophrenia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Dr. Guy Rouleau's laboratory, McGill University | Jan 01, 2014 | COS with PDD NOS, Asperger's Disorder, Separation Anxiety Disorder - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
T;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at