rs886037771
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_017909.4(RMND1):c.1303C>T(p.Leu435Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
RMND1
NM_017909.4 missense
NM_017909.4 missense
Scores
10
3
1
Clinical Significance
Conservation
PhyloP100: 9.42
Genes affected
RMND1 (HGNC:21176): (required for meiotic nuclear division 1 homolog) The protein encoded by this gene belongs to the evolutionary conserved sif2 family of proteins that share the DUF155 domain in common. This protein is thought to be localized in the mitochondria and involved in mitochondrial translation. Mutations in this gene are associated with combined oxidative phosphorylation deficiency-11. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.904
PP5
?
Variant 6-151405734-G-A is Pathogenic according to our data. Variant chr6-151405734-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 225256.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-151405734-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RMND1 | NM_017909.4 | c.1303C>T | p.Leu435Phe | missense_variant | 11/12 | ENST00000444024.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RMND1 | ENST00000444024.3 | c.1303C>T | p.Leu435Phe | missense_variant | 11/12 | 3 | NM_017909.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 24
GnomAD4 exome
Cov.:
24
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Mitochondrial disease Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Wellcome Centre for Mitochondrial Research, Newcastle University | Dec 22, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
Polyphen
D;D;.
Vest4
0.95, 0.96
MutPred
Loss of catalytic residue at L435 (P = 0.0702);Loss of catalytic residue at L435 (P = 0.0702);.;
MVP
0.77
MPC
0.84
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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