5-154966745-C-T

Position:

chr5-154966745-C-T

Variant summary

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

The NM_014180.4(MRPL22):c.469C>T(p.Arg157Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000568 in 1,614,154 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 0 hom. )

Consequence

MRPL22
NM_014180.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.586

Variant links:

Genes affected

MRPL22 (HGNC:14480): (mitochondrial ribosomal protein L22) 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 39S subunit protein that belongs to the L22 ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 4q. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MRPL22 links:

MRPL22 (HGNC:):

MRPL22 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=0.12740219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL22	NM_014180.4 linkuse as main transcript	c.469C>T	p.Arg157Cys	missense_variant	7/7	ENST00000523037.6	NP_054899.2	Q9NWU5-1
MRPL22	NM_001014990.3 linkuse as main transcript	c.229C>T	p.Arg77Cys	missense_variant	6/6		NP_001014990.1	Q9NWU5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL22	ENST00000523037.6 linkuse as main transcript	c.469C>T	p.Arg157Cys	missense_variant	7/7	1	NM_014180.4	ENSP00000431040.1		Q9NWU5-1

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000445

AC:

112

AN:

251408

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.000721

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000590

AC:

862

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000569

AC XY:

414

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.000701

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000361

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000617

Hom.:

Bravo

AF:

0.000295

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000494

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000711

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

Nov 20, 2024

The c.469C>T (p.R157C) alteration is located in exon 7 (coding exon 7) of the MRPL22 gene. This alteration results from a C to T substitution at nucleotide position 469, causing the arginine (R) at amino acid position 157 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;.;.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Pathogenic

3.7

H;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-5.2

D;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.018

D;D;D;D

Sift4G

Benign

0.094

T;T;T;T

Polyphen

1.0

D;.;.;.

Vest4

0.26

MVP

0.78

MPC

0.36

ClinPred

0.21

GERP RS

-3.4

Varity_R

0.20

gMVP

0.66

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