Genetic Variant NM_181514.2:c.125A>T (chr11-68900569-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_181514.2(MRPL21):c.125A>T(p.Gln42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q42R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

MRPL21
NM_181514.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.76

Publications

1 publications found

Variant links:

Genes affected

MRPL21 (HGNC:14479): (mitochondrial ribosomal protein L21) 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. Multiple transcript variants encoding different isoforms were identified through sequence analysis although some may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Jul 2008]

MRPL21 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30307543).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181514.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPL21	NM_181514.2	MANE Select	c.125A>T	p.Gln42Leu	missense	Exon 2 of 7	NP_852615.1	Q7Z2W9-1
MRPL21	NM_181515.2		c.-144A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_852616.1	Q7Z2W9-2
MRPL21	NM_181515.2		c.-144A>T		5_prime_UTR	Exon 2 of 7	NP_852616.1	Q7Z2W9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRPL21	ENST00000362034.7	TSL:1 MANE Select	c.125A>T	p.Gln42Leu	missense	Exon 2 of 7	ENSP00000354580.2	Q7Z2W9-1
MRPL21	ENST00000567045.5	TSL:2	c.-144A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000457859.1	H3BUY0
MRPL21	ENST00000450904.6	TSL:2	c.-144A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	ENSP00000389400.2	Q7Z2W9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.039

Eigen

Benign

0.016

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.63

M_CAP

Benign

0.012

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.7

PhyloP100

2.8

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.3

REVEL

Benign

0.12

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.054

Polyphen

0.84

Vest4

0.56

MutPred

0.14

Loss of MoRF binding (P = 0.1064)

MVP

0.39

MPC

0.41

ClinPred

0.85

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.61

Mutation Taster

=275/25

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over