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GeneBe

3-12839399-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000994.4(RPL32):c.228G>C(p.Lys76Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RPL32
NM_000994.4 missense

Scores

4
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPL32NM_000994.4 linkuse as main transcriptc.228G>C p.Lys76Asn missense_variant 3/4 ENST00000429711.7
RPL32NM_001007073.1 linkuse as main transcriptc.228G>C p.Lys76Asn missense_variant 3/4
RPL32NM_001007074.1 linkuse as main transcriptc.228G>C p.Lys76Asn missense_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPL32ENST00000429711.7 linkuse as main transcriptc.228G>C p.Lys76Asn missense_variant 3/41 NM_000994.4 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152214
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461826
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727210
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152214
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74360
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:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 15, 2023The c.228G>C (p.K76N) alteration is located in exon 2 (coding exon 2) of the RPL32 gene. This alteration results from a G to C substitution at nucleotide position 228, causing the lysine (K) at amino acid position 76 to be replaced by an asparagine (N). 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
Pathogenic
0.98
BayesDel_addAF
Uncertain
0.050
T
BayesDel_noAF
Benign
-0.17
Cadd
Uncertain
25
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.42
T;T;T;T;T;T
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Benign
0.033
D
MetaRNN
Uncertain
0.64
D;D;D;D;D;D
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Uncertain
2.6
M;M;.;M;M;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-4.9
D;D;D;D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.028
D;D;D;D;D;D
Sift4G
Benign
0.068
T;T;T;T;T;.
Polyphen
0.068
B;B;.;B;B;.
Vest4
0.86
MutPred
0.54
Loss of methylation at K76 (P = 2e-04);Loss of methylation at K76 (P = 2e-04);.;Loss of methylation at K76 (P = 2e-04);Loss of methylation at K76 (P = 2e-04);Loss of methylation at K76 (P = 2e-04);
MVP
0.33
MPC
1.7
ClinPred
0.99
D
GERP RS
4.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.86
gMVP
0.38

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: rs1353375513; hg19: chr3-12880898; API