chr12-41188727-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.272C>T​(p.Ser91Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000585 in 1,554,482 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

PDZRN4
NM_001164595.2 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.427
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=0.06918457).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PDZRN4NM_001164595.2 linkuse as main transcriptc.272C>T p.Ser91Leu missense_variant 1/10 ENST00000402685.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PDZRN4ENST00000402685.7 linkuse as main transcriptc.272C>T p.Ser91Leu missense_variant 1/102 NM_001164595.2 P1Q6ZMN7-1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152020
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000483
AC:
8
AN:
165666
Hom.:
0
AF XY:
0.0000539
AC XY:
5
AN XY:
92736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000172
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:
0.0000404
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000606
AC:
85
AN:
1402350
Hom.:
0
Cov.:
32
AF XY:
0.0000633
AC XY:
44
AN XY:
694950
show subpopulations
Gnomad4 AFR exome
AF:
0.0000331
Gnomad4 AMR exome
AF:
0.000148
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000125
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000686
Gnomad4 OTH exome
AF:
0.0000343
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152132
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000589
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000180
AC:
2

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 GeneticsNov 05, 2021The c.272C>T (p.S91L) 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 272, causing the serine (S) at amino acid position 91 to be replaced by a leucine (L). 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
0.16
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0079
T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.069
N
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.069
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
0.54
N
REVEL
Benign
0.027
Sift
Benign
0.034
D
Sift4G
Benign
0.22
T
Vest4
0.19
MVP
0.43
MPC
0.80
ClinPred
0.16
T
GERP RS
0.88
Varity_R
0.035
gMVP
0.22

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: rs537582782; hg19: chr12-41582529; COSMIC: COSV68416586; API