chr3-12839399-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000994.4(RPL32):āc.228G>Cā(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 (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
RPL32
NM_000994.4 missense
NM_000994.4 missense
Scores
4
11
4
Clinical Significance
Conservation
PhyloP100: 5.84
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]
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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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPL32 | NM_000994.4 | c.228G>C | p.Lys76Asn | missense_variant | 3/4 | ENST00000429711.7 | NP_000985.1 | |
RPL32 | NM_001007073.1 | c.228G>C | p.Lys76Asn | missense_variant | 3/4 | NP_001007074.1 | ||
RPL32 | NM_001007074.1 | c.228G>C | p.Lys76Asn | missense_variant | 2/3 | NP_001007075.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPL32 | ENST00000429711.7 | c.228G>C | p.Lys76Asn | missense_variant | 3/4 | 1 | NM_000994.4 | ENSP00000416429 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727210
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74360
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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 submitter | clinical testing | Ambry Genetics | May 15, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;.;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;.;M;M;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;.
Polyphen
B;B;.;B;B;.
Vest4
MutPred
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
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at