chr21-34172341-G-A

Position:

• chr21-34172341-G-A

Variant summary

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

The ENST00000362077.4(ENSG00000272657):​n.295-43159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,188 control chromosomes in the GnomAD database, including 2,281 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 0.13 (2281 hom., cov: 32)
• Consequence: ENSG00000272657 ENST00000362077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

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]

LINC00310 (HGNC:16414): (long intergenic non-protein coding RNA 310)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 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.295-43159G>A		intron_variant		3		ENSP00000520522.1
LINC00310	ENST00000630751.2	n.129+14489G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20395 AN: 152070 Hom.: 2279 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0613

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.134 AC: 20434 AN: 152188 Hom.: 2281 Cov.: 32 AF XY: 0.134 AC XY: 9945 AN XY: 74414

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.0695

Gnomad4 ASJ AF: 0.0613

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0762 Hom.: 396

Bravo AF: 0.138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7277241; hg19: chr21-35544641;