rs12403795

Variant names:

• chr1-150305958-C-T
• rs12403795
• NM_031901.6:c.84-2090C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPS21	NM_031901.6	c.84-2090C>T		intron_variant	Intron 2 of 2	ENST00000614145.5	NP_114107.2
MRPS21	NM_018997.4	c.84-2090C>T		intron_variant	Intron 1 of 1		NP_061870.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRPS21	ENST00000614145.5	c.84-2090C>T		intron_variant	Intron 2 of 2	1	NM_031901.6	ENSP00000480129.1
MRPS21	ENST00000581066.2	c.84-2090C>T		intron_variant	Intron 1 of 1	1		ENSP00000461930.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19767 AN: 152094 Hom.: 1861 Cov.: 32

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.: 32 AF XY: 0.134 AC XY: 9962 AN XY: 74408

Gnomad4 AFR AF: 0.0318

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.0837

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.135

Alfa AF: 0.147 Hom.: 2473

Bravo AF: 0.135

Asia WGS AF: 0.242 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs12403795; hg19: chr1-150278389;