rs9978407

Positions:

• chr21-34246337-G-A

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 0.134 in 152,128 control chromosomes in the GnomAD database, including 1,476 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 (1476 hom., cov: 32)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.34246337G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272657	ENST00000362077.4	n.336-16483G>A		intron_variant		3		ENSP00000520522.1
ENSG00000214955	ENST00000427022.1	n.312-16483G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20372 AN: 152010 Hom.: 1477 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.134 AC: 20376 AN: 152128 Hom.: 1476 Cov.: 32 AF XY: 0.131 AC XY: 9706 AN XY: 74372

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0659

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.125

Alfa AF: 0.132 Hom.: 352

Bravo AF: 0.133

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9978407; hg19: chr21-35618638;