3-139006133-C-T

Variant summary

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

The NM_001134659.1(PRR23A):​c.136G>A​(p.Glu46Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,392,442 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: not found (cov: 31)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

PRR23A
NM_001134659.1 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.227
Variant links:
Genes affected
PRR23A (HGNC:37172): (proline rich 23A)
MRPS22 (HGNC:14508): (mitochondrial ribosomal protein S22) 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 28S subunit protein that does not seem to have a counterpart in prokaryotic and fungal-mitochondrial ribosomes. This gene lies telomeric of and is transcribed in the opposite direction from the forkhead box L2 gene. A pseudogene corresponding to this gene is found on chromosome Xq. [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=0.18875071).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRR23ANM_001134659.1 linkuse as main transcriptc.136G>A p.Glu46Lys missense_variant 1/1 ENST00000383163.4 NP_001128131.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRR23AENST00000383163.4 linkuse as main transcriptc.136G>A p.Glu46Lys missense_variant 1/1 NM_001134659.1 ENSP00000372649 P1
MRPS22ENST00000495075.5 linkuse as main transcriptc.-143+38C>T intron_variant 1 ENSP00000418008 P4P82650-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000707
AC:
1
AN:
141502
Hom.:
0
AF XY:
0.0000131
AC XY:
1
AN XY:
76564
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000186
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.18e-7
AC:
1
AN:
1392442
Hom.:
0
Cov.:
35
AF XY:
0.00000146
AC XY:
1
AN XY:
686972
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:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 GeneticsAug 17, 2022The c.136G>A (p.E46K) alteration is located in exon 1 (coding exon 1) of the PRR23A gene. This alteration results from a G to A substitution at nucleotide position 136, causing the glutamic acid (E) at amino acid position 46 to be replaced by a lysine (K). 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
0.17
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.0046
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-2.5
D
REVEL
Benign
0.15
Sift
Benign
0.053
T
Sift4G
Benign
0.083
T
Polyphen
0.95
P
Vest4
0.10
MutPred
0.53
Gain of ubiquitination at E46 (P = 0.0014);
MVP
0.067
MPC
1.4
ClinPred
0.70
D
GERP RS
0.53
Varity_R
0.071
gMVP
0.21

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: rs1435963423; hg19: chr3-138724975; API