rs268674

Variant summary

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

The NM_181882.3(PRX):​c.3394G>T​(p.Gly1132Trp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1132R) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PRX
NM_181882.3 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.347
Variant links:
Genes affected
PRX (HGNC:13797): (periaxin) This gene encodes a protein involved in peripheral nerve myelin upkeep. The encoded protein contains 2 PDZ domains which were named after PSD95 (post synaptic density protein), DlgA (Drosophila disc large tumor suppressor), and ZO1 (a mammalian tight junction protein). Two alternatively spliced transcript variants have been described for this gene which encode different protein isoforms and which are targeted differently in the Schwann cell. Mutations in this gene cause Charcot-Marie-Tooth neuoropathy, type 4F and Dejerine-Sottas neuropathy. [provided by RefSeq, Jul 2008]

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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=0.21482208).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRXNM_181882.3 linkuse as main transcriptc.3394G>T p.Gly1132Trp missense_variant 7/7 ENST00000324001.8
PRXNM_001411127.1 linkuse as main transcriptc.3679G>T p.Gly1227Trp missense_variant 7/7
PRXXM_017027047.2 linkuse as main transcriptc.3292G>T p.Gly1098Trp missense_variant 4/4
PRXNM_020956.2 linkuse as main transcriptc.*3599G>T 3_prime_UTR_variant 6/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRXENST00000324001.8 linkuse as main transcriptc.3394G>T p.Gly1132Trp missense_variant 7/71 NM_181882.3 A2Q9BXM0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
96
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.27
T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.39
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.10
Sift
Uncertain
0.014
D
Sift4G
Uncertain
0.023
D
Polyphen
0.90
P
Vest4
0.21
MutPred
0.56
Loss of disorder (P = 0.0054);
MVP
0.32
MPC
0.27
ClinPred
0.54
D
GERP RS
3.6
Varity_R
0.096
gMVP
0.15

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: rs268674; hg19: chr19-40900865; API