chr21-34354455-C-T

Position:

• chr21-34354455-C-T

Variant summary

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

The ENST00000440403.2(ENSG00000225555):​n.1287G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,144 control chromosomes in the GnomAD database, including 4,098 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 0.21 (4098 hom., cov: 32)
• Consequence: ENSG00000225555 ENST00000440403.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

ENSG00000225555 (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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105372791	NR_188571.1	n.1285G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000225555	ENST00000440403.2	n.1287G>A		non_coding_transcript_exon_variant	3/3	3
ENSG00000272657	ENST00000362077.4	n.514-5451C>T		intron_variant		3		ENSP00000520522.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31491 AN: 152026 Hom.: 4091 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.207 AC: 31543 AN: 152144 Hom.: 4098 Cov.: 32 AF XY: 0.206 AC XY: 15346 AN XY: 74382

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.196

Alfa AF: 0.155 Hom.: 2107

Bravo AF: 0.214

Asia WGS AF: 0.216 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.1
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2834465; hg19: chr21-35726754;