rs2834467

Positions:

• chr21-34356981-A-G
• chr21-34356981-A-T

Variant summary

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

The ENST00000362077.4(ENSG00000272657):​n.514-2925A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,750 control chromosomes in the GnomAD database, including 33,558 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 0.64 (33558 hom., cov: 29)
• Consequence: ENSG00000272657 ENST00000362077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

Genes affected

ENSG00000272657 (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]

ENSG00000225555 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105372791	NR_188571.1	n.853-2094T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272657	ENST00000362077.4	n.514-2925A>G		intron_variant		3		ENSP00000520522.1
ENSG00000225555	ENST00000440403.2	n.855-2094T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97646 AN: 151632 Hom.: 33562 Cov.: 29

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.735

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.644 AC: 97662 AN: 151750 Hom.: 33558 Cov.: 29 AF XY: 0.650 AC XY: 48183 AN XY: 74150

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.677

Alfa AF: 0.693 Hom.: 17696

Bravo AF: 0.634

Asia WGS AF: 0.741 AC: 2579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.47
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2834467; hg19: chr21-35729280;