NM_031901.6:c.83+3917C>T

Variant names:

• chr1-150298366-C-T
• rs7511649
• NM_031901.6:c.83+3917C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS21	NM_031901.6	MANE Select	c.83+3917C>T		intron	N/A	NP_114107.2
	MRPS21	NM_018997.4		c.83+3917C>T		intron	N/A	NP_061870.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS21	ENST00000614145.5	TSL:1 MANE Select	c.83+3917C>T		intron	N/A	ENSP00000480129.1
	MRPS21	ENST00000581066.2	TSL:1	c.83+3917C>T		intron	N/A	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

African (AFR) AF: 0.947 AC: 39356 AN: 41550

American (AMR) AF: 0.846 AC: 12933 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2485 AN: 3470

East Asian (EAS) AF: 0.818 AC: 4228 AN: 5168

South Asian (SAS) AF: 0.789 AC: 3802 AN: 4820

European-Finnish (FIN) AF: 0.764 AC: 8079 AN: 10570

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54231 AN: 68016

Other (OTH) AF: 0.808 AC: 1705 AN: 2110

Alfa AF: 0.822 Hom.: 17145

Bravo AF: 0.850

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
PhyloP100		0.43

Splicing

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

Other links and lift over

dbSNP: rs7511649; hg19: chr1-150270791;