2-27800253-T-C

Position:

• chr2-27800253-T-C

Variant summary

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

The NM_022128.3(RBKS):​c.796-18465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,926 control chromosomes in the GnomAD database, including 7,075 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 0.29 (7075 hom., cov: 30)
• Consequence: RBKS NM_022128.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBKS	NM_022128.3	c.796-18465A>G		intron_variant		ENST00000302188.8	NP_071411.1
RBKS	NM_001287580.2	c.595-18465A>G		intron_variant			NP_001274509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBKS	ENST00000302188.8	c.796-18465A>G		intron_variant		1	NM_022128.3	ENSP00000306817.3
RBKS	ENST00000449378.1	n.*1723-18465A>G		intron_variant		1		ENSP00000413789.1
MRPL33	ENST00000448427.1	n.164+17559T>C		intron_variant		4		ENSP00000407385.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43543 AN: 151808 Hom.: 7067 Cov.: 30

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.287 AC: 43593 AN: 151926 Hom.: 7075 Cov.: 30 AF XY: 0.297 AC XY: 22050 AN XY: 74246

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.270

Alfa AF: 0.238 Hom.: 2244

Bravo AF: 0.303

Asia WGS AF: 0.467 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.7
DANN	Benign	0.58

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: rs11127125; hg19: chr2-28023120;