6-151433213-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4

The NM_017909.4(RMND1):​c.631G>A​(p.Val211Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,459,260 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 pathogenic (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

RMND1
NM_017909.4 missense

Scores

1
9
9

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 4.24
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-151433213-C-T is Pathogenic according to our data. Variant chr6-151433213-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 225260.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.3512208). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RMND1NM_017909.4 linkc.631G>A p.Val211Met missense_variant Exon 4 of 12 ENST00000444024.3 NP_060379.2 Q9NWS8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RMND1ENST00000444024.3 linkc.631G>A p.Val211Met missense_variant Exon 4 of 12 3 NM_017909.4 ENSP00000412708.2 Q9NWS8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
249916
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135100
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000480
AC:
7
AN:
1459260
Hom.:
0
Cov.:
29
AF XY:
0.00000689
AC XY:
5
AN XY:
726050
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Mitochondrial disease Pathogenic:1
Dec 22, 2015
Wellcome Centre for Mitochondrial Research, Newcastle University
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Combined oxidative phosphorylation defect type 11 Pathogenic:1
Feb 20, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Benign
-0.049
T
BayesDel_noAF
Benign
-0.21
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T;T;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.93
.;D;D
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.35
T;T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Uncertain
2.4
M;M;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.3
.;N;.
REVEL
Benign
0.13
Sift
Uncertain
0.018
.;D;.
Sift4G
Uncertain
0.059
.;T;T
Polyphen
0.99
D;D;.
Vest4
0.90, 0.73
MutPred
0.36
Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;
MVP
0.36
MPC
0.80
ClinPred
0.88
D
GERP RS
5.2
Varity_R
0.16
gMVP
0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs771894262; hg19: chr6-151754348; API