12-41188849-G-C

Variant summary

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

The NM_001164595.2(PDZRN4):ā€‹c.394G>Cā€‹(p.Gly132Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000269 in 1,261,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G132S) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000067 ( 0 hom., cov: 31)
Exomes š‘“: 0.000030 ( 0 hom. )

Consequence

PDZRN4
NM_001164595.2 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.682
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=0.15231696).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDZRN4NM_001164595.2 linkuse as main transcriptc.394G>C p.Gly132Arg missense_variant 1/10 ENST00000402685.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDZRN4ENST00000402685.7 linkuse as main transcriptc.394G>C p.Gly132Arg missense_variant 1/102 NM_001164595.2 P1Q6ZMN7-1

Frequencies

GnomAD3 genomes
AF:
0.00000671
AC:
1
AN:
148946
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000149
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000297
AC:
33
AN:
1112856
Hom.:
0
Cov.:
30
AF XY:
0.0000358
AC XY:
19
AN XY:
530482
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000125
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000309
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000320
Gnomad4 OTH exome
AF:
0.0000224
GnomAD4 genome
AF:
0.00000671
AC:
1
AN:
148946
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
1
AN XY:
72590
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000149
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000530
Hom.:
0
Bravo
AF:
0.0000416

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 GeneticsJan 24, 2024The c.394G>C (p.G132R) alteration is located in exon 1 (coding exon 1) of the PDZRN4 gene. This alteration results from a G to C substitution at nucleotide position 394, causing the glycine (G) at amino acid position 132 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
0.13
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
15
DANN
Benign
0.60
DEOGEN2
Benign
0.0045
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.46
T
M_CAP
Pathogenic
0.32
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
-0.69
N
MutationTaster
Benign
0.99
N
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.39
N
REVEL
Benign
0.041
Sift
Benign
0.25
T
Sift4G
Uncertain
0.0090
D
Vest4
0.11
MutPred
0.39
Gain of catalytic residue at C133 (P = 0.0103);
MVP
0.64
MPC
1.1
ClinPred
0.042
T
GERP RS
0.53
Varity_R
0.058
gMVP
0.18

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

LitVar

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

Other links and lift over

dbSNP: rs572012656; hg19: chr12-41582651; API