dbSNP rs371243093: PRX:p.Pro180Pro (chr19-40397812-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_181882.3(PRX):c.540G>A(p.Pro180Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000569 in 1,585,618 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 2 hom. )

Consequence

PRX
NM_181882.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.43

Publications

1 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: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-40397812-C-T is Benign according to our data. Variant chr19-40397812-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 379671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AD,AR gene

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.540G>A	p.Pro180Pro	synonymous	Exon 7 of 7	NP_870998.2	Q9BXM0-1
PRX	NM_001411127.1		c.825G>A	p.Pro275Pro	synonymous	Exon 7 of 7	NP_001398056.1	A0A669KBF1
PRX	NM_020956.2		c.*745G>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.540G>A	p.Pro180Pro	synonymous	Exon 7 of 7	ENSP00000326018.6	Q9BXM0-1
PRX	ENST00000291825.11	TSL:1	c.*745G>A		3_prime_UTR	Exon 6 of 6	ENSP00000291825.6	Q9BXM0-2
PRX	ENST00000674005.2		c.825G>A	p.Pro275Pro	synonymous	Exon 7 of 7	ENSP00000501261.1	A0A669KBF1

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000479

AC:

AN:

194334

AF XY:

0.000492

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000432

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000666

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000866

Gnomad OTH exome

AF:

0.000797

GnomAD4 exome

AF:

0.000592

AC:

848

AN:

1433272

Hom.:

Cov.:

AF XY:

0.000624

AC XY:

443

AN XY:

710264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33244

American (AMR)

AF:

0.000283

AC:

AN:

38806

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25448

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38828

South Asian (SAS)

AF:

0.000230

AC:

AN:

82666

European-Finnish (FIN)

AF:

0.000119

AC:

AN:

50262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.000707

AC:

777

AN:

1098882

Other (OTH)

AF:

0.000572

AC:

AN:

59416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

117

175

234

292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<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:

0.000361

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41594

American (AMR)

AF:

0.000196

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000691

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000850

Hom.:

Bravo

AF:

0.000423

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Charcot-Marie-Tooth disease (1)

Charcot-Marie-Tooth disease type 4 (1)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.6

(source)

DANN

Benign

0.80

PhyloP100

-1.4

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over