chr21-34344892-T-C

Variant names:

• chr21-34344892-T-C
• rs2834462
• ENST00000362077.4:n.514-15014T>C

Variant summary

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

The ENST00000362077.4(ENSG00000272657):​n.514-15014T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 151,986 control chromosomes in the GnomAD database, including 38,420 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 0.71 (38420 hom., cov: 31)
• Consequence: ENSG00000272657 ENST00000362077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 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.514-15014T>C		intron_variant	Intron 5 of 5	3		ENSP00000520522.1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107261 AN: 151868 Hom.: 38379 Cov.: 31

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.706 AC: 107358 AN: 151986 Hom.: 38420 Cov.: 31 AF XY: 0.707 AC XY: 52548 AN XY: 74282

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.751

Gnomad4 ASJ AF: 0.651

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.690

Alfa AF: 0.687 Hom.: 23764

Bravo AF: 0.711

Asia WGS AF: 0.596 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.031
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2834462; hg19: chr21-35717191;