chr12-41188859-C-G

Variant summary

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

The NM_001164595.2(PDZRN4):ā€‹c.404C>Gā€‹(p.Pro135Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000354 in 1,243,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000034 ( 0 hom., cov: 31)
Exomes š‘“: 0.000036 ( 0 hom. )

Consequence

PDZRN4
NM_001164595.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24
Variant links:
Genes affected
PDZRN4 (HGNC:30552): (PDZ domain containing ring finger 4) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08049983).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDZRN4NM_001164595.2 linkuse as main transcriptc.404C>G p.Pro135Arg missense_variant 1/10 ENST00000402685.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDZRN4ENST00000402685.7 linkuse as main transcriptc.404C>G p.Pro135Arg missense_variant 1/102 NM_001164595.2 P1Q6ZMN7-1

Frequencies

GnomAD3 genomes
AF:
0.0000337
AC:
5
AN:
148248
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000488
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000300
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000356
AC:
39
AN:
1095116
Hom.:
0
Cov.:
29
AF XY:
0.0000345
AC XY:
18
AN XY:
521260
show subpopulations
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:
0.0000421
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000337
AC:
5
AN:
148356
Hom.:
0
Cov.:
31
AF XY:
0.0000415
AC XY:
3
AN XY:
72330
show subpopulations
Gnomad4 AFR
AF:
0.0000487
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000300
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 29, 2023The c.404C>G (p.P135R) alteration is located in exon 1 (coding exon 1) of the PDZRN4 gene. This alteration results from a C to G substitution at nucleotide position 404, causing the proline (P) at amino acid position 135 to be replaced by an arginine (R). 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
0.075
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
11
DANN
Benign
0.81
DEOGEN2
Benign
0.0095
T
Eigen
Benign
-0.88
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.054
N
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.080
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
0.41
N
REVEL
Benign
0.064
Sift
Benign
0.41
T
Sift4G
Benign
0.13
T
Vest4
0.18
MutPred
0.38
Gain of catalytic residue at G132 (P = 0);
MVP
0.48
MPC
0.94
ClinPred
0.065
T
GERP RS
0.56
Varity_R
0.046
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs539005475; hg19: chr12-41582661; API