chr21-34261230-A-G

Variant names:

• chr21-34261230-A-G
• rs973754
• ENST00000362077.4:n.336-1590A>G

Variant summary

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

The ENST00000362077.4(ENSG00000272657):​n.336-1590A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,158 control chromosomes in the GnomAD database, including 3,411 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 0.18 (3411 hom., cov: 32)
• Consequence: ENSG00000272657 ENST00000362077.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 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.336-1590A>G		intron_variant	Intron 3 of 5	3		ENSP00000520522.1
ENSG00000214955	ENST00000427022.1	n.312-1590A>G		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27832 AN: 152040 Hom.: 3411 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0662

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.183 AC: 27870 AN: 152158 Hom.: 3411 Cov.: 32 AF XY: 0.179 AC XY: 13287 AN XY: 74398

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0662

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.155

Alfa AF: 0.141 Hom.: 1014

Bravo AF: 0.189

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs973754; hg19: chr21-35633530;