21-34073744-G-C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_032476.4(MRPS6):c.44G>C(p.Arg15Pro) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000726 in 1,376,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R15Q) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 7.3e-7 ( 0 hom. )
Consequence
MRPS6
NM_032476.4 missense, splice_region
NM_032476.4 missense, splice_region
Scores
3
10
6
Splicing: ADA: 0.5318
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.84
Publications
0 publications found
Genes affected
SLC5A3 (HGNC:11038): (solute carrier family 5 member 3) Enables potassium channel regulator activity and transmembrane transporter binding activity. Predicted to be involved in inositol metabolic process; monosaccharide transmembrane transport; and myo-inositol import across plasma membrane. Predicted to act upstream of or within several processes, including peripheral nervous system development; positive regulation of reactive oxygen species biosynthetic process; and regulation of respiratory gaseous exchange. Located in plasma membrane. Part of perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
MRPS6 (HGNC:14051): (mitochondrial ribosomal protein S6) 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 28S subunit protein that belongs to the ribosomal protein S6P family. Pseudogenes corresponding to this gene are found on chromosomes 1p and 12q. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.751
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| SLC5A3 | NM_006933.7 | c.-338G>C | splice_region_variant | Exon 1 of 2 | ENST00000381151.5 | NP_008864.4 | ||
| MRPS6 | NM_032476.4 | c.44G>C | p.Arg15Pro | missense_variant, splice_region_variant | Exon 1 of 3 | ENST00000399312.3 | NP_115865.1 | |
| SLC5A3 | NM_006933.7 | c.-338G>C | 5_prime_UTR_variant | Exon 1 of 2 | ENST00000381151.5 | NP_008864.4 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SLC5A3 | ENST00000381151.5 | c.-338G>C | splice_region_variant | Exon 1 of 2 | 1 | NM_006933.7 | ENSP00000370543.3 | |||
| MRPS6 | ENST00000399312.3 | c.44G>C | p.Arg15Pro | missense_variant, splice_region_variant | Exon 1 of 3 | 1 | NM_032476.4 | ENSP00000382250.2 | ||
| ENSG00000293606 | ENST00000715811.1 | c.-338G>C | splice_region_variant | Exon 1 of 4 | ENSP00000520523.1 | |||||
| SLC5A3 | ENST00000381151.5 | c.-338G>C | 5_prime_UTR_variant | Exon 1 of 2 | 1 | NM_006933.7 | ENSP00000370543.3 | |||
| ENSG00000293606 | ENST00000715811.1 | c.-338G>C | 5_prime_UTR_variant | Exon 1 of 4 | ENSP00000520523.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD4 exome AF: 7.26e-7 AC: 1AN: 1376470Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 684984 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1376470
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
684984
show subpopulations
African (AFR)
AF:
AC:
0
AN:
27940
American (AMR)
AF:
AC:
0
AN:
38498
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
22932
East Asian (EAS)
AF:
AC:
0
AN:
32388
South Asian (SAS)
AF:
AC:
0
AN:
81208
European-Finnish (FIN)
AF:
AC:
0
AN:
48984
Middle Eastern (MID)
AF:
AC:
0
AN:
4630
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1064786
Other (OTH)
AF:
AC:
0
AN:
55104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.875
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
30
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0029);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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