rs8128316

Positions:

• chr21-34349261-C-T

Variant summary

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

The variant allele was found at a frequency of 0.538 in 151,794 control chromosomes in the GnomAD database, including 22,567 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 0.54 (22567 hom., cov: 31)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

Genes affected

(HGNC:):

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.34349261C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272657	ENST00000362077.4	n.514-10645C>T		intron_variant		3		ENSP00000520522.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81573 AN: 151676 Hom.: 22535 Cov.: 31

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.612

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.538 AC: 81655 AN: 151794 Hom.: 22567 Cov.: 31 AF XY: 0.542 AC XY: 40171 AN XY: 74170

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.503

Alfa AF: 0.491 Hom.: 25889

Bravo AF: 0.546

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8128316; hg19: chr21-35721560;