rs2834455

Variant names:

• chr21-34337459-T-C
• rs2834455
• ENST00000362077.4:n.514-22447T>C

Variant summary

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

The ENST00000362077.4(ENSG00000272657):​n.514-22447T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,026 control chromosomes in the GnomAD database, including 5,773 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 0.22 (5773 hom., cov: 32)
• Consequence: ENSG00000272657 ENST00000362077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000272657	ENST00000362077.4	n.514-22447T>C		intron_variant	Intron 5 of 5	3		ENSP00000520522.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32681 AN: 151908 Hom.: 5743 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0923

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.216 AC: 32770 AN: 152026 Hom.: 5773 Cov.: 32 AF XY: 0.211 AC XY: 15717 AN XY: 74324

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0926

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.213

Alfa AF: 0.126 Hom.: 2405

Bravo AF: 0.228

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.23
DANN	Benign	0.14

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2834455; hg19: chr21-35709758;