19-40394517-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_181882.3(PRX):c.3835G>A(p.Val1279Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,448,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. V1279L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PRX
NM_181882.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.917

Publications

0 publications found

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]

PRX Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease type 4
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Charcot-Marie-Tooth disease type 4F
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
Charcot-Marie-Tooth disease type 3
Inheritance: AD, AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

PRX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26856804).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181882.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRX	NM_181882.3	MANE Select	c.3835G>A	p.Val1279Met	missense	Exon 7 of 7	NP_870998.2	Q9BXM0-1
PRX	NM_001411127.1		c.4120G>A	p.Val1374Met	missense	Exon 7 of 7	NP_001398056.1	A0A669KBF1
PRX	NM_020956.2		c.*4040G>A		3_prime_UTR	Exon 6 of 6	NP_066007.1	Q9BXM0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRX	ENST00000324001.8	TSL:1 MANE Select	c.3835G>A	p.Val1279Met	missense	Exon 7 of 7	ENSP00000326018.6	Q9BXM0-1
PRX	ENST00000291825.11	TSL:1	c.*4040G>A		3_prime_UTR	Exon 6 of 6	ENSP00000291825.6	Q9BXM0-2
PRX	ENST00000674005.2		c.4120G>A	p.Val1374Met	missense	Exon 7 of 7	ENSP00000501261.1	A0A669KBF1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000449

AC:

AN:

222790

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000483

AC:

AN:

1448158

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719816

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33128

American (AMR)

AF:

0.00

AC:

AN:

42924

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25798

East Asian (EAS)

AF:

0.00

AC:

AN:

38782

South Asian (SAS)

AF:

0.0000473

AC:

AN:

84622

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51126

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1106220

Other (OTH)

AF:

0.00

AC:

AN:

59808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000826

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.81

M_CAP

Benign

0.017

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

0.92

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.6

REVEL

Benign

0.098

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.054

Polyphen

1.0

Vest4

0.35

MutPred

0.20

Loss of sheet (P = 0.0315)

MVP

0.42

MPC

0.68

ClinPred

0.62

GERP RS

2.6

Varity_R

0.10

gMVP

0.21

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over