rs1244182671

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181514.2(MRPL21):c.540C>A(p.Phe180Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MRPL21
NM_181514.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

Publications

0 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1763894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL21	NM_181514.2 link	c.540C>A	p.Phe180Leu	missense_variant	Exon 6 of 7	ENST00000362034.7	NP_852615.1	Q7Z2W9-1
MRPL21	NM_181515.2 link	c.285C>A	p.Phe95Leu	missense_variant	Exon 6 of 7		NP_852616.1	Q7Z2W9-2A0A024R5G7
MRPL21	XM_005273823.5 link	c.540C>A	p.Phe180Leu	missense_variant	Exon 6 of 6		XP_005273880.1	B4DXI4
MRPL21	XR_247190.5 link	n.643C>A		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.540C>A	p.Phe180Leu	missense_variant	Exon 6 of 7	1	NM_181514.2	ENSP00000354580.2		Q7Z2W9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000803

AC:

AN:

249066

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460476

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726418

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.0000349

AC:

AN:

85996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111206

Other (OTH)

AF:

0.00

AC:

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Nov 12, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.540C>A (p.F180L) alteration is located in exon 6 (coding exon 6) of the MRPL21 gene. This alteration results from a C to A substitution at nucleotide position 540, causing the phenylalanine (F) at amino acid position 180 to be replaced by a leucine (L). 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

0.87

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;T;T

Eigen

Benign

0.052

Eigen_PC

Benign

0.033

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.72

T;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.6

.;M;.

PhyloP100

1.9

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Benign

0.067

Sift

Benign

0.052

T;D;D

Sift4G

Uncertain

0.054

T;D;D

Polyphen

0.56

.;P;.

Vest4

0.29

MutPred

0.46

.;Loss of methylation at K181 (P = 0.033);.;

MVP

0.55

MPC

0.21

ClinPred

0.92

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.41

gMVP

0.41

Mutation Taster

=59/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over