rs7511649

Positions:

• chr1-150298366-C-T

Variant summary

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

The NM_031901.6(MRPS21):​c.83+3917C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,200 control chromosomes in the GnomAD database, including 53,974 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 0.84 (53974 hom., cov: 32)
• Consequence: MRPS21 NM_031901.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRPS21	NM_031901.6	c.83+3917C>T		intron_variant		ENST00000614145.5	NP_114107.2
MRPS21	NM_018997.4	c.83+3917C>T		intron_variant			NP_061870.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRPS21	ENST00000614145.5	c.83+3917C>T		intron_variant		1	NM_031901.6	ENSP00000480129.1
MRPS21	ENST00000581066.2	c.83+3917C>T		intron_variant		1		ENSP00000461930.1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127638 AN: 152082 Hom.: 53923 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.839 AC: 127746 AN: 152200 Hom.: 53974 Cov.: 32 AF XY: 0.838 AC XY: 62310 AN XY: 74396

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.789

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.808

Alfa AF: 0.828 Hom.: 8826

Bravo AF: 0.850

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7511649; hg19: chr1-150270791;