Variant 9-101390735-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_019051.3(MRPL50):c.208T>G(p.Leu70Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MRPL50
NM_019051.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10688943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPL50	NM_019051.3 link	c.208T>G	p.Leu70Val	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 link	c.208T>G	p.Leu70Val	missense_variant	2/2	1	NM_019051.3	ENSP00000363999.4		Q8N5N7-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

147382

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00111

Gnomad SAS

AF:

0.000716

Gnomad FIN

AF:

0.000503

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000599

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00339

AC:

3106

AN:

917318

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

1449

AN XY:

468058

show subpopulations

Gnomad4 AFR exome

AF:

0.00467

Gnomad4 AMR exome

AF:

0.000971

Gnomad4 ASJ exome

AF:

0.00421

Gnomad4 EAS exome

AF:

0.00460

Gnomad4 SAS exome

AF:

0.000740

Gnomad4 FIN exome

AF:

0.00501

Gnomad4 NFE exome

AF:

0.00357

Gnomad4 OTH exome

AF:

0.00459

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000183

AC:

AN:

147540

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

AN XY:

72056

show subpopulations

Gnomad4 AFR

AF:

0.000148

Gnomad4 AMR

AF:

0.000203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00111

Gnomad4 SAS

AF:

0.000712

Gnomad4 FIN

AF:

0.000503

Gnomad4 NFE

AF:

0.0000599

Gnomad4 OTH

AF:

0.00

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

Aug 13, 2021

The c.208T>G (p.L70V) alteration is located in exon 2 (coding exon 2) of the MRPL50 gene. This alteration results from a T to G substitution at nucleotide position 208, causing the leucine (L) at amino acid position 70 to be replaced by a valine (V). 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

0.069

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0073

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.72

M_CAP

Benign

0.0075

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.77

REVEL

Benign

0.014

Sift

Benign

0.15

Sift4G

Benign

0.070

Polyphen

0.12

Vest4

0.14

MutPred

0.45

Loss of helix (P = 0.1299);

MVP

0.16

MPC

0.021

ClinPred

0.11

GERP RS

-1.0

Varity_R

0.18

gMVP

0.29

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