21-34344892-T-C

Position:

• chr21-34344892-T-C

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 0.706 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: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00

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=-0.99).
• 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/exons	MANE	Protein	UniProt
		n.34344892T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272657	ENST00000362077.4	n.514-15014T>C		intron_variant		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;