rs772371895

Variant summary

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

The NM_031903.3(MRPL32):​c.5C>G​(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 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. A2V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

MRPL32
NM_031903.3 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.719
Variant links:
Genes affected
MRPL32 (HGNC:14035): (mitochondrial ribosomal protein L32) 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 that belongs to the L32 ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome Xp. [provided by RefSeq, Jul 2008]
PSMA2 (HGNC:9531): (proteasome 20S subunit alpha 2) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. [provided by RefSeq, Jul 2008]

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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=0.3194102).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL32NM_031903.3 linkc.5C>G p.Ala2Gly missense_variant Exon 1 of 3 ENST00000223324.3 NP_114109.1 Q9BYC8A4D1V4
MRPL32NR_156497.1 linkn.16C>G non_coding_transcript_exon_variant Exon 1 of 4
PSMA2NM_002787.5 linkc.-233G>C upstream_gene_variant ENST00000223321.9 NP_002778.1 P25787A0A024RA52

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL32ENST00000223324.3 linkc.5C>G p.Ala2Gly missense_variant Exon 1 of 3 1 NM_031903.3 ENSP00000223324.2 Q9BYC8
PSMA2ENST00000223321.9 linkc.-233G>C upstream_gene_variant 1 NM_002787.5 ENSP00000223321.4 P25787
ENSG00000256646ENST00000677581.1 linkc.-390G>C upstream_gene_variant ENSP00000504213.1 A0A7I2YQP7

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
248944
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134578
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000656
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1455392
Hom.:
0
Cov.:
32
AF XY:
0.00000553
AC XY:
4
AN XY:
722976
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000450
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.024
T
Eigen
Benign
0.068
Eigen_PC
Benign
-0.038
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.45
T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.67
N
REVEL
Benign
0.12
Sift
Uncertain
0.018
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.36
MutPred
0.34
Gain of relative solvent accessibility (P = 0.0479);
MVP
0.40
MPC
0.19
ClinPred
0.88
D
GERP RS
3.2
Varity_R
0.071
gMVP
0.58

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: rs772371895; hg19: chr7-42971990; API