rs873811

Variant names:

• chr21-34171167-C-T
• rs873811
• ENST00000362077.5:n.186-44333C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000362077.5(MRPS6):​n.186-44333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,136 control chromosomes in the GnomAD database, including 2,270 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 (2270 hom., cov: 33)
• Consequence: MRPS6 ENST00000362077.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 4 publications found

Genes affected

MRPS6 (HGNC:14051): (mitochondrial ribosomal protein S6) 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 S6P family. Pseudogenes corresponding to this gene are found on chromosomes 1p and 12q. [provided by RefSeq, Jul 2008]

LINC00310 (HGNC:16414): (long intergenic non-protein coding RNA 310)

ENSG00000304893 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000362077.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPS6	ENST00000362077.5	TSL:3	n.186-44333C>T		intron	N/A	ENSP00000520522.1	A0ABB0MUY8
	LINC00310	ENST00000630751.2	TSL:5	n.129+13315C>T		intron	N/A
	MRPS6	ENST00000715810.1		n.186-9544C>T		intron	N/A	ENSP00000520521.1	A0ABB0MV00

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20334 AN: 152018 Hom.: 2268 Cov.: 33

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0614

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0532

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.134 AC: 20374 AN: 152136 Hom.: 2270 Cov.: 33 AF XY: 0.133 AC XY: 9914 AN XY: 74392

African (AFR) AF: 0.299 AC: 12390 AN: 41466

American (AMR) AF: 0.0694 AC: 1062 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0614 AC: 213 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1041 AN: 5174

South Asian (SAS) AF: 0.129 AC: 621 AN: 4820

European-Finnish (FIN) AF: 0.103 AC: 1091 AN: 10588

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0532 AC: 3621 AN: 68002

Other (OTH) AF: 0.123 AC: 261 AN: 2114

Alfa AF: 0.0801 Hom.: 4002

Bravo AF: 0.138

Asia WGS AF: 0.207 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.4
DANN	Benign	0.79
PhyloP100		-0.14

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs873811;

hg19: chr21-35543467;