rs749677650

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_145729.3(MRPL24):c.162G>T(p.Trp54Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MRPL24
NM_145729.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.07

Variant links:

Genes affected

MRPL24 (HGNC:14037): (mitochondrial ribosomal protein L24) 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 which is more than twice the size of its E.coli counterpart (EcoL24). Sequence analysis identified two transcript variants that encode the same protein. [provided by RefSeq, Jul 2008]

MRPL24 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.822

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL24	NM_145729.3 link	c.162G>T	p.Trp54Cys	missense_variant	Exon 2 of 6	ENST00000361531.6	NP_663781.1	Q96A35
MRPL24	NM_024540.4 link	c.162G>T	p.Trp54Cys	missense_variant	Exon 2 of 6		NP_078816.2	Q96A35
MRPL24	XM_011509981.3 link	c.162G>T	p.Trp54Cys	missense_variant	Exon 2 of 6		XP_011508283.1	Q96A35
MRPL24	XM_011509982.3 link	c.162G>T	p.Trp54Cys	missense_variant	Exon 2 of 6		XP_011508284.1	Q96A35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL24	ENST00000361531.6 link	c.162G>T	p.Trp54Cys	missense_variant	Exon 2 of 6	1	NM_145729.3	ENSP00000354525.2		Q96A35

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727242

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.162G>T (p.W54C) alteration is located in exon 2 (coding exon 1) of the MRPL24 gene. This alteration results from a G to T substitution at nucleotide position 162, causing the tryptophan (W) at amino acid position 54 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

Pathogenic

0.83

BayesDel_addAF

Pathogenic

0.46

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;T;T;.;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

.;T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Pathogenic

0.82

D;D;D;D;D

MetaSVM

Benign

-0.30

MutationAssessor

Uncertain

2.6

M;M;.;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-12

D;D;D;D;D

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;.;D

Polyphen

1.0

D;D;.;.;.

Vest4

0.92

MutPred

0.64

Loss of catalytic residue at W54 (P = 0.0056);Loss of catalytic residue at W54 (P = 0.0056);Loss of catalytic residue at W54 (P = 0.0056);Loss of catalytic residue at W54 (P = 0.0056);Loss of catalytic residue at W54 (P = 0.0056);

MVP

0.36

MPC

1.1

ClinPred

1.0

GERP RS

5.5

Varity_R

0.95

gMVP

0.91

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