rs1057519316
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001329556.3(REEP6):āc.404T>Cā(p.Leu135Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ).
Frequency
Genomes: not found (cov: 34)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
REEP6
NM_001329556.3 missense
NM_001329556.3 missense
Scores
10
6
2
Clinical Significance
Conservation
PhyloP100: 5.86
Genes affected
REEP6 (HGNC:30078): (receptor accessory protein 6) The protein encoded by this gene may be involved in the transport of receptors from the endoplasmic reticulum (ER) to the cell surface. The encoded protein may also play a role in regulating ER membrane structure. This gene is required for the proper development of retinal rods and photoreceptors, with defects in this gene being associated with retinitis pigmentosa 77. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.986
PP5
?
Variant 19-1496340-T-C is Pathogenic according to our data. Variant chr19-1496340-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 374989.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-1496340-T-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
REEP6 | NM_001329556.3 | c.404T>C | p.Leu135Pro | missense_variant | 4/6 | ENST00000395479.10 | |
REEP6 | NM_138393.4 | c.404T>C | p.Leu135Pro | missense_variant | 4/5 | ENST00000233596.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
REEP6 | ENST00000395479.10 | c.404T>C | p.Leu135Pro | missense_variant | 4/6 | 3 | NM_001329556.3 | ||
REEP6 | ENST00000233596.8 | c.404T>C | p.Leu135Pro | missense_variant | 4/5 | 1 | NM_138393.4 | P1 | |
REEP6 | ENST00000395484.4 | c.188T>C | p.Leu63Pro | missense_variant, NMD_transcript_variant | 2/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460520Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726488
GnomAD4 exome
AF:
AC:
1
AN:
1460520
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
726488
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 15, 2023 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects REEP6 function (PMID: 27889058, 28475715). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 374989). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 27889058). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 135 of the REEP6 protein (p.Leu135Pro). - |
Retinitis pigmentosa 77 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 19, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Pathogenic
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0663);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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