rs2834463

Variant names:

• chr21-34345168-G-A
• rs2834463
• ENST00000362077.4:n.514-14738G>A

Your query was ambiguous. Multiple possible variants found:

• chr21-34345168-G-A
• chr21-34345168-G-C

Variant summary

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

The ENST00000362077.4(ENSG00000272657):​n.514-14738G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,096 control chromosomes in the GnomAD database, including 33,164 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 0.66 (33164 hom., cov: 32)
• Consequence: ENSG00000272657 ENST00000362077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.711 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.514-14738G>A		intron_variant	Intron 5 of 5	3		ENSP00000520522.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99991 AN: 151978 Hom.: 33136 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.658 AC: 100076 AN: 152096 Hom.: 33164 Cov.: 32 AF XY: 0.659 AC XY: 49004 AN XY: 74346

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.646

Alfa AF: 0.651 Hom.: 17924

Bravo AF: 0.661

Asia WGS AF: 0.579 AC: 2014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2834463; hg19: chr21-35717467;