dbSNP rs12403795: MRPS21:c.84-2090C>T (chr1-150305958-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031901.6(MRPS21):c.84-2090C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,214 control chromosomes in the GnomAD database, including 1,867 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1867 hom., cov: 32)

Consequence

MRPS21
NM_031901.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.290

Publications

13 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031901.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS21	NM_031901.6	MANE Select	c.84-2090C>T		intron	N/A	NP_114107.2	P82921
	MRPS21	NM_018997.4		c.84-2090C>T		intron	N/A	NP_061870.2	P82921

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MRPS21	ENST00000614145.5	TSL:1 MANE Select	c.84-2090C>T	intron	N/A	ENSP00000480129.1	P82921
MRPS21	ENST00000581066.2	TSL:1	c.84-2090C>T	intron	N/A	ENSP00000461930.1	P82921
MRPS21	ENST00000877736.1		c.84-2090C>T	intron	N/A	ENSP00000547795.1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19767

AN:

152094

Hom.:

1861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0318

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.0837

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.130

AC:

19785

AN:

152214

Hom.:

1867

Cov.:

AF XY:

0.134

AC XY:

9962

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0318

AC:

1320

AN:

41562

American (AMR)

AF:

0.278

AC:

4237

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

374

AN:

3472

East Asian (EAS)

AF:

0.252

AC:

1305

AN:

5170

South Asian (SAS)

AF:

0.332

AC:

1601

AN:

4822

European-Finnish (FIN)

AF:

0.0837

AC:

888

AN:

10604

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9652

AN:

68002

Other (OTH)

AF:

0.135

AC:

285

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

836

1672

2507

3343

4179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.146

Hom.:

3087

Bravo

AF:

0.135

Asia WGS

AF:

0.242

AC:

844

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.5

(source)

DANN

Benign

0.51

PhyloP100

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over