Variant chr3-139006133-C-T details in Genebe, Genetics Data Aggregator

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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.227

Variant links:

Genes affected

PRR23A (HGNC:37172): (proline rich 23A)

PRR23A links:

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]

MRPS22 links:

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
PRR23A	NM_001134659.1 linkuse as main transcript	c.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
PRR23A	ENST00000383163.4 linkuse as main transcript	c.136G>A	p.Glu46Lys	missense_variant	1/1		NM_001134659.1	ENSP00000372649	P1
MRPS22	ENST00000495075.5 linkuse as main transcript	c.-143+38C>T		intron_variant		1		ENSP00000418008	P4	P82650-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000707

AC:

AN:

141502

Hom.:

AF XY:

0.0000131

AC XY:

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:

AN:

1392442

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

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.:

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

Aug 17, 2022

The 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

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.55

M_CAP

Benign

0.016

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.15

Sift

Benign

0.053

Sift4G

Benign

0.083

Polyphen

0.95

Vest4

0.10

MutPred

0.53

Gain of ubiquitination at E46 (P = 0.0014);

MVP

0.067

MPC

1.4

ClinPred

0.70

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over