Menu
GeneBe

3-12839403-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000994.4(RPL32):c.224G>A(p.Arg75Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

RPL32
NM_000994.4 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59
Variant links:
Genes affected
RPL32 (HGNC:10336): (ribosomal protein L32) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L32E family of ribosomal proteins. It is located in the cytoplasm. Although some studies have mapped this gene to 3q13.3-q21, it is believed to map to 3p25-p24. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternatively spliced transcript variants encoding the same protein have been observed for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08203894).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL32NM_000994.4 linkuse as main transcriptc.224G>A p.Arg75Gln missense_variant 3/4 ENST00000429711.7
RPL32NM_001007073.1 linkuse as main transcriptc.224G>A p.Arg75Gln missense_variant 3/4
RPL32NM_001007074.1 linkuse as main transcriptc.224G>A p.Arg75Gln missense_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL32ENST00000429711.7 linkuse as main transcriptc.224G>A p.Arg75Gln missense_variant 3/41 NM_000994.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152200
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:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000123
AC:
31
AN:
251470
Hom.:
0
AF XY:
0.000132
AC XY:
18
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000924
Gnomad SAS exome
AF:
0.000457
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000397
AC:
58
AN:
1461834
Hom.:
0
Cov.:
31
AF XY:
0.0000509
AC XY:
37
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.000487
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152318
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.000115
AC:
14

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 17, 2023The c.224G>A (p.R75Q) alteration is located in exon 2 (coding exon 2) of the RPL32 gene. This alteration results from a G to A substitution at nucleotide position 224, causing the arginine (R) at amino acid position 75 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
Uncertain
0.53
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.30
Cadd
Uncertain
25
Dann
Uncertain
1.0
DEOGEN2
Benign
0.14
T;T;T;T;T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.058
FATHMM_MKL
Uncertain
0.82
D
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.082
T;T;T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.78
N;N;.;N;N;.
MutationTaster
Benign
1.0
D;N;N;N;N;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-2.1
N;N;N;N;N;N
REVEL
Benign
0.20
Sift
Benign
0.092
T;T;T;T;T;T
Sift4G
Benign
0.38
T;T;T;T;T;.
Polyphen
0.0020
B;B;.;B;B;.
Vest4
0.29
MutPred
0.30
Loss of MoRF binding (P = 0.0254);Loss of MoRF binding (P = 0.0254);.;Loss of MoRF binding (P = 0.0254);Loss of MoRF binding (P = 0.0254);Loss of MoRF binding (P = 0.0254);
MVP
0.39
MPC
0.78
ClinPred
0.099
T
GERP RS
4.0
Varity_R
0.19
gMVP
0.25

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: rs777726300; hg19: chr3-12880902; COSMIC: COSV55994790; COSMIC: COSV55994790; API