Genetic Variant NM_181882.3:c.133C>A (chr19-40403757-G-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_181882.3(PRX):c.133C>A(p.Arg45Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,435,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R45R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PRX
NM_181882.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

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), 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: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP7

Synonymous conserved (PhyloP=1.99 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRX	NM_181882.3 link	c.133C>A	p.Arg45Arg	synonymous_variant	Exon 5 of 7	ENST00000324001.8	NP_870998.2	Q9BXM0-1
PRX	NM_001411127.1 link	c.418C>A	p.Arg140Arg	synonymous_variant	Exon 5 of 7		NP_001398056.1
PRX	NM_020956.2 link	c.133C>A	p.Arg45Arg	synonymous_variant	Exon 5 of 6		NP_066007.1	Q9BXM0-2
PRX	XM_017027047.2 link	c.-100C>A		upstream_gene_variant			XP_016882536.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRX	ENST00000324001.8 link	c.133C>A	p.Arg45Arg	synonymous_variant	Exon 5 of 7	1	NM_181882.3	ENSP00000326018.6		Q9BXM0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1435778

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32626

American (AMR)

AF:

0.00

AC:

AN:

42028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25626

East Asian (EAS)

AF:

0.00

AC:

AN:

37792

South Asian (SAS)

AF:

0.00

AC:

AN:

82660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5556

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1100480

Other (OTH)

AF:

0.00

AC:

AN:

59302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

2.0

PromoterAI

-0.042

Neutral

(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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over