7-42934967-C-T

Variant summary

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

The NM_031903.3(MRPL32):​c.143C>T​(p.Ala48Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000834 in 1,438,286 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: not found (cov: 32)
Exomes 𝑓: 0.0000083 ( 1 hom. )

Consequence

MRPL32
NM_031903.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61
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]

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=0.2908641).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRPL32NM_031903.3 linkc.143C>T p.Ala48Val missense_variant Exon 2 of 3 ENST00000223324.3 NP_114109.1 Q9BYC8A4D1V4
MRPL32NR_156497.1 linkn.154C>T non_coding_transcript_exon_variant Exon 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRPL32ENST00000223324.3 linkc.143C>T p.Ala48Val missense_variant Exon 2 of 3 1 NM_031903.3 ENSP00000223324.2 Q9BYC8
MRPL32ENST00000432845.1 linkn.143C>T non_coding_transcript_exon_variant Exon 2 of 3 2 ENSP00000415581.1 B3KQX1
MRPL32ENST00000413995.1 linkn.-56C>T upstream_gene_variant 2 ENSP00000391562.1 H7BZU9
MRPL32ENST00000496564.1 linkn.-76C>T upstream_gene_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000171
AC:
4
AN:
233830
Hom.:
1
AF XY:
0.0000316
AC XY:
4
AN XY:
126648
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 SAS exome
AF:
0.000149
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000834
AC:
12
AN:
1438286
Hom.:
1
Cov.:
31
AF XY:
0.0000126
AC XY:
9
AN XY:
714960
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000134
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.143C>T (p.A48V) alteration is located in exon 2 (coding exon 2) of the MRPL32 gene. This alteration results from a C to T substitution at nucleotide position 143, causing the alanine (A) at amino acid position 48 to be replaced by a valine (V). 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
0.12
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.19
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.29
T
MetaSVM
Benign
-0.83
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.0
D
REVEL
Benign
0.15
Sift
Benign
0.074
T
Sift4G
Benign
0.076
T
Polyphen
0.38
B
Vest4
0.15
MutPred
0.83
Gain of sheet (P = 0.0344);
MVP
0.31
MPC
0.078
ClinPred
0.80
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.26
gMVP
0.77

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: rs769978247; hg19: chr7-42974566; API