chr12-41188505-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001164595.2(PDZRN4):ā€‹c.50A>Gā€‹(p.Glu17Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,438,724 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˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

PDZRN4
NM_001164595.2 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3410043).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDZRN4NM_001164595.2 linkuse as main transcriptc.50A>G p.Glu17Gly missense_variant 1/10 ENST00000402685.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDZRN4ENST00000402685.7 linkuse as main transcriptc.50A>G p.Glu17Gly missense_variant 1/102 NM_001164595.2 P1Q6ZMN7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.95e-7
AC:
1
AN:
1438724
Hom.:
0
Cov.:
32
AF XY:
0.00000140
AC XY:
1
AN XY:
715390
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:
0.00
Gnomad4 OTH exome
AF:
0.0000167
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 GeneticsDec 07, 2021The c.50A>G (p.E17G) alteration is located in exon 1 (coding exon 1) of the PDZRN4 gene. This alteration results from a A to G substitution at nucleotide position 50, causing the glutamic acid (E) at amino acid position 17 to be replaced by a glycine (G). 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
0.19
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.014
T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.47
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.071
D
MetaRNN
Benign
0.34
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
0.99
N
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.93
N
REVEL
Benign
0.043
Sift
Uncertain
0.0090
D
Sift4G
Uncertain
0.025
D
Vest4
0.15
MutPred
0.46
Gain of catalytic residue at K19 (P = 0.0157);
MVP
0.66
MPC
1.1
ClinPred
0.41
T
GERP RS
1.4
Varity_R
0.066
gMVP
0.27

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: chr12-41582307; API