chr11-68900582-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181514.2(MRPL21):​c.112A>G​(p.Arg38Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

MRPL21
NM_181514.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.290

Publications

0 publications found
Variant links:
Genes affected
MRPL21 (HGNC:14479): (mitochondrial ribosomal protein L21) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. Multiple transcript variants encoding different isoforms were identified through sequence analysis although some may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.049243033).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL21NM_181514.2 linkc.112A>G p.Arg38Gly missense_variant Exon 2 of 7 ENST00000362034.7 NP_852615.1 Q7Z2W9-1
MRPL21XM_005273823.5 linkc.112A>G p.Arg38Gly missense_variant Exon 2 of 6 XP_005273880.1 B4DXI4
MRPL21XR_247190.5 linkn.134A>G non_coding_transcript_exon_variant Exon 2 of 6
MRPL21NM_181515.2 linkc.-157A>G 5_prime_UTR_variant Exon 2 of 7 NP_852616.1 Q7Z2W9-2A0A024R5G7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL21ENST00000362034.7 linkc.112A>G p.Arg38Gly missense_variant Exon 2 of 7 1 NM_181514.2 ENSP00000354580.2 Q7Z2W9-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152168
Hom.:
0
Cov.:
33
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:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.0000756
AC:
19
AN:
251472
AF XY:
0.0000957
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000527
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1461658
Hom.:
0
Cov.:
30
AF XY:
0.0000413
AC XY:
30
AN XY:
727150
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26128
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.000209
AC:
18
AN:
86252
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
0.000694
AC:
4
AN:
5766
European-Non Finnish (NFE)
AF:
0.0000198
AC:
22
AN:
1111824
Other (OTH)
AF:
0.000116
AC:
7
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.445
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152286
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74470
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41556
American (AMR)
AF:
0.00
AC:
0
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5178
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68026
Other (OTH)
AF:
0.000473
AC:
1
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.0000868
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000824
AC:
10
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 12, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.112A>G (p.R38G) alteration is located in exon 2 (coding exon 2) of the MRPL21 gene. This alteration results from a A to G substitution at nucleotide position 112, causing the arginine (R) at amino acid position 38 to be replaced by a glycine (G). 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
0.078
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
12
DANN
Benign
0.83
DEOGEN2
Benign
0.014
T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.049
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.6
M
PhyloP100
0.29
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.016
Sift
Benign
0.31
T
Sift4G
Benign
0.080
T
Polyphen
0.0030
B
Vest4
0.18
MutPred
0.30
Loss of stability (P = 0.0044);
MVP
0.20
MPC
0.21
ClinPred
0.040
T
GERP RS
0.63
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.082
gMVP
0.43
Mutation Taster
=93/7
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs754802573; hg19: chr11-68668050; API