1-150294448-A-G

Position:

chr1-150294448-A-G

Variant summary

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

The NM_031901.6(MRPS21):c.82A>G(p.Arg28Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000223 in 1,610,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MRPS21
NM_031901.6 missense, splice_region

Scores

Splicing: ADA: 0.9977

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97

Variant links:

Genes affected

MRPS21 (HGNC:14046): (mitochondrial ribosomal protein S21) 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 28S subunit protein that belongs to the ribosomal protein S21P family. Pseudogenes corresponding to this gene are found on chromosomes 1p, 1q, 9p, 10p, 10q, 16q, and 17q. Available sequence data analyses identified splice variants that differ in the 5' UTR; both transcripts encode the same protein. [provided by RefSeq, Jul 2008]

MRPS21 links:

Genome browser will be placed here

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
MRPS21	NM_031901.6 link	c.82A>G	p.Arg28Gly	missense_variant, splice_region_variant	2/3	ENST00000614145.5	NP_114107.2	P82921Q99768
MRPS21	NM_018997.4 link	c.82A>G	p.Arg28Gly	missense_variant, splice_region_variant	1/2		NP_061870.2	P82921Q99768

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS21	ENST00000614145.5 link	c.82A>G	p.Arg28Gly	missense_variant, splice_region_variant	2/3	1	NM_031901.6	ENSP00000480129.1		P82921
MRPS21	ENST00000581066.2 link	c.82A>G	p.Arg28Gly	missense_variant, splice_region_variant	1/2	1		ENSP00000461930.1		P82921

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249074

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134810

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1458740

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

725888

show subpopulations

Gnomad4 AFR exome

AF:

0.000449

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000332

GnomAD4 genome

AF:

0.000118

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000410

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.00000824

AC:

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

Oct 01, 2024

The c.82A>G (p.R28G) alteration is located in exon 1 (coding exon 1) of the MRPS21 gene. This alteration results from a A to G substitution at nucleotide position 82, causing the arginine (R) at amino acid position 28 to be replaced by a glycine (G). 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

0.19

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.77

.;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.41

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.54

Sift4G

Benign

0.065

T;T

Polyphen

0.074

B;B

Vest4

0.82

MutPred

0.62

Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);

MVP

0.40

ClinPred

0.86

GERP RS

5.4

Varity_R

0.48

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.060

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