3-139019926-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001013650.2(PRR23B):c.736G>A(p.Ala246Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000491 in 1,608,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A246P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

PRR23B
NM_001013650.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.817

Publications

5 publications found

Variant links:

Genes affected

PRR23B (HGNC:33764): (proline rich 23B)

PRR23B 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 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hypotonia with lactic acidemia and hyperammonemia
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
46 XX gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
ovarian dysgenesis 7
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MRPS22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08171111).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013650.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR23B	NM_001013650.2	MANE Select	c.736G>A	p.Ala246Thr	missense	Exon 1 of 1	NP_001013672.1	Q6ZRT6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR23B	ENST00000329447.5	TSL:6 MANE Select	c.736G>A	p.Ala246Thr	missense	Exon 1 of 1	ENSP00000328768.5	Q6ZRT6
	MRPS22	ENST00000495075.5	TSL:1	c.-143+13831C>T		intron	N/A	ENSP00000418008.1	P82650-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000100

AC:

AN:

239170

AF XY:

0.000131

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000494

AC:

AN:

1456078

Hom.:

Cov.:

AF XY:

0.0000663

AC XY:

AN XY:

723806

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.000113

AC:

AN:

44268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25682

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84880

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52896

Middle Eastern (MID)

AF:

0.00159

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.0000460

AC:

AN:

1109420

Other (OTH)

AF:

0.0000998

AC:

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41532

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67958

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000824

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000909

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.6

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0074

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.37

M_CAP

Benign

0.0019

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.77

PhyloP100

0.82

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.51

REVEL

Benign

0.092

Sift

Benign

0.29

Sift4G

Benign

0.55

Polyphen

0.99

Vest4

0.023

MVP

0.014

MPC

0.52

ClinPred

0.054

GERP RS

3.6

Varity_R

0.030

gMVP

0.050

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over