Variant 5-154966793-G-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_014180.4(MRPL22):c.517G>T(p.Val173Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,878 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: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MRPL22
NM_014180.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.49

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:

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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=0.23220372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL22	NM_014180.4 linkuse as main transcript	c.517G>T	p.Val173Leu	missense_variant	7/7	ENST00000523037.6	NP_054899.2	Q9NWU5-1
MRPL22	NM_001014990.3 linkuse as main transcript	c.277G>T	p.Val93Leu	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.517G>T	p.Val173Leu	missense_variant	7/7	1	NM_014180.4	ENSP00000431040.1		Q9NWU5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251332

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135824

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ExAC

AF:

0.00000824

AC:

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

Mar 25, 2024

The c.517G>T (p.V173L) alteration is located in exon 7 (coding exon 7) of the MRPL22 gene. This alteration results from a G to T substitution at nucleotide position 517, causing the valine (V) at amino acid position 173 to be replaced by a leucine (L). 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

0.29

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

T;.;.;T

Eigen

Benign

-0.0049

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.088

T;T;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.0090

B;.;.;.

Vest4

0.36

MutPred

0.33

Loss of ubiquitination at K171 (P = 0.1037);.;.;.;

MVP

0.46

MPC

0.13

ClinPred

0.61

GERP RS

4.9

Varity_R

0.81

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