chr2-27828084-C-T

Variant names:

• chr2-27828084-C-T
• rs9679543
• NM_022128.3:c.607-329G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022128.3(RBKS):​c.607-329G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,016 control chromosomes in the GnomAD database, including 10,421 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 0.34 (10421 hom., cov: 32)
• Consequence: RBKS NM_022128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 1 publications found

Genes affected

RBKS (HGNC:30325): (ribokinase) This gene encodes a member of the carbohydrate kinase PfkB family. The encoded protein phosphorylates ribose to form ribose-5-phosphate in the presence of ATP and magnesium as a first step in ribose metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

MRPL33 (HGNC:14487): (mitochondrial ribosomal protein L33) 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 39S subunit protein. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022128.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBKS	NM_022128.3	MANE Select	c.607-329G>A		intron	N/A	NP_071411.1	Q9H477-1
	RBKS	NM_001287580.2		c.406-329G>A		intron	N/A	NP_001274509.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBKS	ENST00000302188.8	TSL:1 MANE Select	c.607-329G>A		intron	N/A	ENSP00000306817.3	Q9H477-1
	RBKS	ENST00000449378.1	TSL:1	n.*1534-329G>A		intron	N/A	ENSP00000413789.1	E7EQ18
	RBKS	ENST00000861376.1		c.442-329G>A		intron	N/A	ENSP00000531435.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50867 AN: 151898 Hom.: 10379 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.335 AC: 50978 AN: 152016 Hom.: 10421 Cov.: 32 AF XY: 0.343 AC XY: 25442 AN XY: 74272

African (AFR) AF: 0.526 AC: 21806 AN: 41462

American (AMR) AF: 0.401 AC: 6119 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3472

East Asian (EAS) AF: 0.630 AC: 3250 AN: 5160

South Asian (SAS) AF: 0.311 AC: 1499 AN: 4822

European-Finnish (FIN) AF: 0.270 AC: 2843 AN: 10546

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.202 AC: 13713 AN: 67978

Other (OTH) AF: 0.298 AC: 629 AN: 2114

Alfa AF: 0.283 Hom.: 2463

Bravo AF: 0.359

Asia WGS AF: 0.481 AC: 1671 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.095
DANN	Benign	0.34
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9679543; hg19: chr2-28050951;