rs58599399
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006262.4(PRPH):c.421G>A(p.Asp141Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000431 in 1,393,282 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.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000043 ( 0 hom. )
Consequence
PRPH
NM_006262.4 missense
NM_006262.4 missense
Scores
1
4
14
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.80
Genes affected
PRPH (HGNC:9461): (peripherin) This gene encodes a cytoskeletal protein found in neurons of the peripheral nervous system. The encoded protein is a type III intermediate filament protein with homology to other cytoskeletal proteins such as desmin, and is a different protein that the peripherin found in photoreceptors. Mutations in this gene have been associated with susceptibility to amyotrophic lateral sclerosis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21736407).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRPH | NM_006262.4 | c.421G>A | p.Asp141Asn | missense_variant | 1/9 | ENST00000257860.9 | NP_006253.2 | |
TROAP-AS1 | NR_120449.1 | n.2451C>T | non_coding_transcript_exon_variant | 6/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRPH | ENST00000257860.9 | c.421G>A | p.Asp141Asn | missense_variant | 1/9 | 1 | NM_006262.4 | ENSP00000257860.4 | ||
PRPH | ENST00000451891.4 | c.100-18G>A | intron_variant | 5 | ENSP00000408897.4 | |||||
TROAP-AS1 | ENST00000553259.1 | n.2451C>T | non_coding_transcript_exon_variant | 6/8 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000431 AC: 6AN: 1393282Hom.: 0 Cov.: 31 AF XY: 0.00000437 AC XY: 3AN XY: 687148
GnomAD4 exome
AF:
AC:
6
AN:
1393282
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
687148
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of MoRF binding (P = 0.0436);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at