19-40394272-TTCCTCCTCCTCC-TTCCTCCTCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_181882.3(PRX):c.4077_4079delGGA(p.Glu1360del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,368,446 control chromosomes in the GnomAD database, including 726 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 139 hom., cov: 32)

Exomes 𝑓: 0.017 ( 587 hom. )

Consequence

PRX
NM_181882.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:4B:8

Conservation

PhyloP100: 1.16

Publications

6 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), Orphanet, Ambry Genetics
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: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_181882.3

BP6

Variant 19-40394272-TTCC-T is Benign according to our data. Variant chr19-40394272-TTCC-T is described in ClinVar as Benign. ClinVar VariationId is 215547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

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
PRX	NM_181882.3	MANE Select	c.4077_4079delGGA	p.Glu1360del	disruptive_inframe_deletion	Exon 7 of 7	NP_870998.2
PRX	NM_001411127.1		c.4362_4364delGGA	p.Glu1455del	disruptive_inframe_deletion	Exon 7 of 7	NP_001398056.1
PRX	NM_020956.2		c.4282_4284delGGA		3_prime_UTR	Exon 6 of 6	NP_066007.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PRX	ENST00000324001.8	TSL:1 MANE Select	c.4077_4079delGGA	p.Glu1360del	disruptive_inframe_deletion	Exon 7 of 7	ENSP00000326018.6
PRX	ENST00000291825.11	TSL:1	c.4282_4284delGGA		3_prime_UTR	Exon 6 of 6	ENSP00000291825.6
PRX	ENST00000674005.2		c.4362_4364delGGA	p.Glu1455del	disruptive_inframe_deletion	Exon 7 of 7	ENSP00000501261.1

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3222

AN:

150898

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00790

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00484

Gnomad OTH

AF:

0.0217

GnomAD2 exomes

AF:

0.0729

AC:

10638

AN:

145830

AF XY:

0.0651

show subpopulations

Gnomad AFR exome

AF:

0.0460

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.0399

Gnomad EAS exome

AF:

0.0149

Gnomad FIN exome

AF:

0.0173

Gnomad NFE exome

AF:

0.0305

Gnomad OTH exome

AF:

0.0639

GnomAD4 exome

AF:

0.0173

AC:

21017

AN:

1217436

Hom.:

587

AF XY:

0.0175

AC XY:

10444

AN XY:

596600

show subpopulations

African (AFR)

AF:

0.0301

AC:

830

AN:

27550

American (AMR)

AF:

0.245

AC:

8676

AN:

35484

Ashkenazi Jewish (ASJ)

AF:

0.0117

AC:

231

AN:

19692

East Asian (EAS)

AF:

0.00356

AC:

109

AN:

30656

South Asian (SAS)

AF:

0.0283

AC:

1477

AN:

52134

European-Finnish (FIN)

AF:

0.00842

AC:

355

AN:

42140

Middle Eastern (MID)

AF:

0.0133

AC:

AN:

4894

European-Non Finnish (NFE)

AF:

0.00872

AC:

8339

AN:

955846

Other (OTH)

AF:

0.0191

AC:

935

AN:

49040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

887

1774

2662

3549

4436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

356

712

1068

1424

1780

<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

AF:

0.0214

AC:

3231

AN:

151010

Hom.:

139

Cov.:

AF XY:

0.0230

AC XY:

1698

AN XY:

73744

show subpopulations

African (AFR)

AF:

0.0246

AC:

1014

AN:

41296

American (AMR)

AF:

0.115

AC:

1756

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00811

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00480

AC:

AN:

10208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00484

AC:

327

AN:

67610

Other (OTH)

AF:

0.0215

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

143

286

428

571

714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0738

Hom.:

Bravo

AF:

0.0340

ClinVar

Significance: Benign

Submissions summary: Uncertain:4Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Aug 13, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Charcot-Marie-Tooth disease

Uncertain:1Benign:1

Aug 14, 2019

Genesis Genome Database

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

Molecular Genetics Laboratory, London Health Sciences Centre

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Charcot-Marie-Tooth disease type 4

Uncertain:1Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 14, 2019

Genesis Genome Database

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

Charcot-Marie-Tooth disease type 5

Uncertain:1

Aug 14, 2019

Genesis Genome Database

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

Charcot-Marie-Tooth disease, type I

Uncertain:1

Aug 14, 2019

Genesis Genome Database

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

Spinocerebellar ataxia 46

Benign:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Charcot-Marie-Tooth disease type 4F

Benign:1

May 24, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=86/14

polymorphism (auto)

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over