dbSNP rs199675137: MRPL21:p.Arg173Thr (chr11-68892925-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181514.2(MRPL21):c.518G>C(p.Arg173Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MRPL21
NM_181514.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.543

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 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=0.1511986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL21	NM_181514.2 link	c.518G>C	p.Arg173Thr	missense_variant	Exon 6 of 7	ENST00000362034.7	NP_852615.1	Q7Z2W9-1
MRPL21	NM_181515.2 link	c.263G>C	p.Arg88Thr	missense_variant	Exon 6 of 7		NP_852616.1	Q7Z2W9-2A0A024R5G7
MRPL21	XM_005273823.5 link	c.518G>C	p.Arg173Thr	missense_variant	Exon 6 of 6		XP_005273880.1	B4DXI4
MRPL21	XR_247190.5 link	n.621G>C		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPL21	ENST00000362034.7 link	c.518G>C	p.Arg173Thr	missense_variant	Exon 6 of 7	1	NM_181514.2	ENSP00000354580.2		Q7Z2W9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461312

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726924

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.096

.;T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.1

.;M;.

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Benign

0.086

Sift

Benign

0.039

D;D;D

Sift4G

Uncertain

0.038

D;D;D

Polyphen

0.35

.;B;.

Vest4

0.34

MutPred

0.59

.;Loss of catalytic residue at R173 (P = 0.0265);.;

MVP

0.25

MPC

0.44

ClinPred

0.43

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.63

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

Computational scores

Splicing

Publications

Other links and lift over