rs2834442

Positions:

• chr21-34318486-T-A
• chr21-34318486-T-C
• chr21-34318486-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000362077.4(ENSG00000272657):​n.513+24730T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 152,084 control chromosomes in the GnomAD database, including 32,479 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 0.65 (32479 hom., cov: 32)
• Consequence: ENSG00000272657 ENST00000362077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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]

ENSG00000214955 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272657	ENST00000362077.4	n.513+24730T>A		intron_variant		3		ENSP00000520522.1
ENSG00000214955	ENST00000427022.1	n.507-6250T>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98963 AN: 151966 Hom.: 32458 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.651 AC: 99039 AN: 152084 Hom.: 32479 Cov.: 32 AF XY: 0.656 AC XY: 48778 AN XY: 74336

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.649

Alfa AF: 0.649 Hom.: 17805

Bravo AF: 0.648

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2834442; hg19: chr21-35690786;