rs9978142

Positions:

• chr21-34279939-A-T
• chr21-34279939-A-G

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 0.15 in 152,170 control chromosomes in the GnomAD database, including 1,850 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 0.15 (1850 hom., cov: 32)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.34279939A>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272657	ENST00000362077.4	n.438-13742A>T		intron_variant		3		ENSP00000520522.1
ENSG00000214955	ENST00000427022.1	n.431-13742A>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22853 AN: 152052 Hom.: 1851 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0659

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.150 AC: 22863 AN: 152170 Hom.: 1850 Cov.: 32 AF XY: 0.146 AC XY: 10828 AN XY: 74386

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0662

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.140

Alfa AF: 0.146 Hom.: 953

Bravo AF: 0.149

Asia WGS AF: 0.0380 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.35
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9978142; hg19: chr21-35652239;