Variant 9-101390485-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019051.3(MRPL50):c.458A>C(p.Lys153Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,124 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MRPL50
NM_019051.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02

Variant links:

Genes affected

MRPL50 (HGNC:16654): (mitochondrial ribosomal protein L50) 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 putative 39S subunit protein and belongs to the L47P ribosomal protein family. Pseudogenes corresponding to this gene are found on chromosomes 2p, 2q, 5p, and 10q. [provided by RefSeq, Jul 2008]

MRPL50 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL50	NM_019051.3 linkuse as main transcript	c.458A>C	p.Lys153Thr	missense_variant	2/2	ENST00000374865.5	NP_061924.1	Q8N5N7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPL50	ENST00000374865.5 linkuse as main transcript	c.458A>C	p.Lys153Thr	missense_variant	2/2	1	NM_019051.3	ENSP00000363999.4		Q8N5N7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725640

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

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:

0.00

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

Dec 20, 2021

The c.458A>C (p.K153T) alteration is located in exon 2 (coding exon 2) of the MRPL50 gene. This alteration results from a A to C substitution at nucleotide position 458, causing the lysine (K) at amino acid position 153 to be replaced by a threonine (T). 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

Uncertain

0.41

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.74

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.7

REVEL

Uncertain

0.32

Sift

Uncertain

0.011

Sift4G

Uncertain

0.014

Polyphen

1.0

Vest4

0.66

MutPred

0.53

Loss of methylation at K153 (P = 0.0112);

MVP

0.57

MPC

0.11

ClinPred

0.96

GERP RS

5.9

Varity_R

0.74

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over