12-41189014-C-T

Variant summary

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

The NM_001164595.2(PDZRN4):​c.559C>T​(p.Leu187Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000244 in 1,556,304 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 1 hom., cov: 31)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PDZRN4
NM_001164595.2 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.347
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=0.07206112).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDZRN4NM_001164595.2 linkuse as main transcriptc.559C>T p.Leu187Phe missense_variant 1/10 ENST00000402685.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDZRN4ENST00000402685.7 linkuse as main transcriptc.559C>T p.Leu187Phe missense_variant 1/102 NM_001164595.2 P1Q6ZMN7-1

Frequencies

GnomAD3 genomes
AF:
0.0000988
AC:
15
AN:
151804
Hom.:
1
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000852
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000367
AC:
6
AN:
163400
Hom.:
0
AF XY:
0.0000561
AC XY:
5
AN XY:
89064
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000222
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000164
AC:
23
AN:
1404382
Hom.:
0
Cov.:
32
AF XY:
0.0000216
AC XY:
15
AN XY:
694994
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000551
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000270
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000170
GnomAD4 genome
AF:
0.0000987
AC:
15
AN:
151922
Hom.:
1
Cov.:
31
AF XY:
0.000108
AC XY:
8
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000851
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000945

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 GeneticsJul 11, 2023The c.559C>T (p.L187F) alteration is located in exon 1 (coding exon 1) of the PDZRN4 gene. This alteration results from a C to T substitution at nucleotide position 559, causing the leucine (L) at amino acid position 187 to be replaced by a phenylalanine (F). 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
-0.42
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.034
T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.62
T
M_CAP
Uncertain
0.092
D
MetaRNN
Benign
0.072
T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
0.93
N
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.72
N
REVEL
Benign
0.098
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.018
D
Vest4
0.11
MutPred
0.38
Loss of sheet (P = 0.0084);
MVP
0.69
MPC
1.0
ClinPred
0.22
T
GERP RS
1.3
Varity_R
0.11
gMVP
0.24

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: rs543178354; hg19: chr12-41582816; API