2-27828084-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBKS	NM_022128.3	c.607-329G>A		intron_variant	Intron 6 of 7	ENST00000302188.8	NP_071411.1
RBKS	NM_001287580.2	c.406-329G>A		intron_variant	Intron 7 of 8		NP_001274509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBKS	ENST00000302188.8	c.607-329G>A		intron_variant	Intron 6 of 7	1	NM_022128.3	ENSP00000306817.3
RBKS	ENST00000449378.1	n.*1534-329G>A		intron_variant	Intron 7 of 8	1		ENSP00000413789.1
RBKS	ENST00000458185.1	c.187-329G>A		intron_variant	Intron 2 of 3	3		ENSP00000393558.1
MRPL33	ENST00000448427.1	n.164+45390C>T		intron_variant	Intron 3 of 5	4		ENSP00000407385.1

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

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.298

Alfa AF: 0.251 Hom.: 971

Bravo AF: 0.359

Asia WGS AF: 0.481 AC: 1671 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.095
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs9679543; hg19: chr2-28050951;