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GeneBe

11-1956389-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021134.4(MRPL23):c.431G>A(p.Arg144Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R144W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 17)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

MRPL23
NM_021134.4 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.090399235).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MRPL23NM_021134.4 linkuse as main transcriptc.431G>A p.Arg144Gln missense_variant 5/5 ENST00000397298.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MRPL23ENST00000397298.8 linkuse as main transcriptc.431G>A p.Arg144Gln missense_variant 5/51 NM_021134.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000153
AC:
2
AN:
131146
Hom.:
0
Cov.:
17
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000168
Gnomad OTH
AF:
0.000581
GnomAD3 exomes
AF:
0.000106
AC:
25
AN:
236708
Hom.:
0
AF XY:
0.0000773
AC XY:
10
AN XY:
129370
show subpopulations
Gnomad AFR exome
AF:
0.0000654
Gnomad AMR exome
AF:
0.0000294
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000213
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000596
AC:
7
AN:
1175278
Hom.:
0
AF XY:
0.00000513
AC XY:
3
AN XY:
584600
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000300
Gnomad4 SAS exome
AF:
0.0000163
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000545
Gnomad4 OTH exome
AF:
0.00
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.0000745
AC:
9
EpiCase
AF:
0.000110
EpiControl
AF:
0.000418

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 15, 2021The c.431G>A (p.R144Q) alteration is located in exon 5 (coding exon 5) of the MRPL23 gene. This alteration results from a G to A substitution at nucleotide position 431, causing the arginine (R) at amino acid position 144 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.51
Cadd
Benign
20
Dann
Uncertain
0.99
DEOGEN2
Benign
0.077
T;T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.27
FATHMM_MKL
Uncertain
0.76
D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.090
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-2.2
N;N
REVEL
Benign
0.10
Sift
Benign
0.058
T;T
Sift4G
Uncertain
0.042
D;D
Polyphen
0.60
P;P
Vest4
0.083
MVP
0.41
MPC
0.28
ClinPred
0.061
T
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.39
gMVP
0.51

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: rs201959963; hg19: chr11-1977619; COSMIC: COSV101203051; COSMIC: COSV101203051; API