1-156737426-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145729.3(MRPL24):​c.623G>A​(p.Arg208Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,603,124 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

MRPL24
NM_145729.3 missense

Scores

4
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.81
Variant links:
Genes affected
MRPL24 (HGNC:14037): (mitochondrial ribosomal protein L24) 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 which is more than twice the size of its E.coli counterpart (EcoL24). Sequence analysis identified two transcript variants that encode the same protein. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29323122).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL24NM_145729.3 linkc.623G>A p.Arg208Gln missense_variant Exon 6 of 6 ENST00000361531.6 NP_663781.1 Q96A35
MRPL24NM_024540.4 linkc.623G>A p.Arg208Gln missense_variant Exon 6 of 6 NP_078816.2 Q96A35
MRPL24XM_011509981.3 linkc.623G>A p.Arg208Gln missense_variant Exon 6 of 6 XP_011508283.1 Q96A35
MRPL24XM_011509982.3 linkc.623G>A p.Arg208Gln missense_variant Exon 6 of 6 XP_011508284.1 Q96A35

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL24ENST00000361531.6 linkc.623G>A p.Arg208Gln missense_variant Exon 6 of 6 1 NM_145729.3 ENSP00000354525.2 Q96A35
MRPL24ENST00000368211.8 linkc.623G>A p.Arg208Gln missense_variant Exon 6 of 6 1 ENSP00000357194.4 Q96A35
MRPL24ENST00000478899.1 linkn.437G>A non_coding_transcript_exon_variant Exon 3 of 3 2
MRPL24ENST00000434558.5 linkc.*104G>A downstream_gene_variant 5 ENSP00000411369.1 X6RJ73

Frequencies

GnomAD3 genomes
AF:
0.000309
AC:
47
AN:
152150
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00292
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.000959
GnomAD3 exomes
AF:
0.000237
AC:
57
AN:
240312
Hom.:
1
AF XY:
0.000246
AC XY:
32
AN XY:
129912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000924
Gnomad ASJ exome
AF:
0.000109
Gnomad EAS exome
AF:
0.000446
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00186
Gnomad NFE exome
AF:
0.0000550
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000986
AC:
143
AN:
1450856
Hom.:
0
Cov.:
31
AF XY:
0.000108
AC XY:
78
AN XY:
721580
show subpopulations
Gnomad4 AFR exome
AF:
0.0000607
Gnomad4 AMR exome
AF:
0.000118
Gnomad4 ASJ exome
AF:
0.0000791
Gnomad4 EAS exome
AF:
0.000655
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00138
Gnomad4 NFE exome
AF:
0.0000199
Gnomad4 OTH exome
AF:
0.000200
GnomAD4 genome
AF:
0.000309
AC:
47
AN:
152268
Hom.:
1
Cov.:
32
AF XY:
0.000416
AC XY:
31
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000772
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00292
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000949
Alfa
AF:
0.0000310
Hom.:
0
Bravo
AF:
0.0000907
ExAC
AF:
0.000132
AC:
16
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 17, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.623G>A (p.R208Q) alteration is located in exon 6 (coding exon 5) of the MRPL24 gene. This alteration results from a G to A substitution at nucleotide position 623, causing the arginine (R) at amino acid position 208 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
0.13
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Pathogenic
0.37
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.86
.;D
M_CAP
Benign
0.052
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Pathogenic
3.2
M;M
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Uncertain
0.63
Sift
Uncertain
0.0070
D;D
Sift4G
Uncertain
0.047
D;D
Polyphen
0.99
D;D
Vest4
0.88
MutPred
0.51
Loss of MoRF binding (P = 0.0416);Loss of MoRF binding (P = 0.0416);
MVP
0.76
MPC
0.40
ClinPred
0.33
T
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.71
gMVP
0.87

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: rs368692555; hg19: chr1-156707218; API