rs577796628
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_181882.3(PRX):c.3831C>T(p.Pro1277=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000356 in 1,601,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P1277P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
PRX
NM_181882.3 synonymous
NM_181882.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.88
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 Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 19-40394521-G-A is Benign according to our data. Variant chr19-40394521-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 697833.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-4.88 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| PRX | NM_181882.3 | c.3831C>T | p.Pro1277= | synonymous_variant | 7/7 | ENST00000324001.8 | |
| PRX | NM_001411127.1 | c.4116C>T | p.Pro1372= | synonymous_variant | 7/7 | ||
| PRX | XM_017027047.2 | c.3729C>T | p.Pro1243= | synonymous_variant | 4/4 | ||
| PRX | NM_020956.2 | c.*4036C>T | 3_prime_UTR_variant | 6/6 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PRX | ENST00000324001.8 | c.3831C>T | p.Pro1277= | synonymous_variant | 7/7 | 1 | NM_181882.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152118Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000313 AC: 7AN: 223946Hom.: 0 AF XY: 0.0000327 AC XY: 4AN XY: 122280
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GnomAD4 exome AF: 0.0000359 AC: 52AN: 1448832Hom.: 0 Cov.: 33 AF XY: 0.0000347 AC XY: 25AN XY: 720210
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74418
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 4 Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 21, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at