chr12-41188733-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001164595.2(PDZRN4):​c.278G>A​(p.Arg93Lys) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

PDZRN4
NM_001164595.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0660
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03825769).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDZRN4NM_001164595.2 linkuse as main transcriptc.278G>A p.Arg93Lys missense_variant 1/10 ENST00000402685.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDZRN4ENST00000402685.7 linkuse as main transcriptc.278G>A p.Arg93Lys missense_variant 1/102 NM_001164595.2 P1Q6ZMN7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 16, 2024The c.278G>A (p.R93K) alteration is located in exon 1 (coding exon 1) of the PDZRN4 gene. This alteration results from a G to A substitution at nucleotide position 278, causing the arginine (R) at amino acid position 93 to be replaced by a lysine (K). 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
0.14
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
8.0
DANN
Benign
0.96
DEOGEN2
Benign
0.0029
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.074
N
LIST_S2
Benign
0.21
T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.038
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
-1.0
N
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
0.69
N
REVEL
Benign
0.038
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Vest4
0.065
MutPred
0.42
Gain of catalytic residue at G89 (P = 5e-04);
MVP
0.25
MPC
0.91
ClinPred
0.071
T
GERP RS
-1.5
Varity_R
0.11
gMVP
0.30

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: chr12-41582535; API