Genetic Variant RXRB:p.Glu64Lys (chr6-33200287-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_021976.5(RXRB):c.190G>A(p.Glu64Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E64Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RXRB
NM_021976.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.28

Publications

0 publications found

Variant links:

Genes affected

RXRB (HGNC:10478): (retinoid X receptor beta) This gene encodes a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the effects of retinoic acid (RA). The encoded protein forms homodimers with the retinoic acid, thyroid hormone, and vitamin D receptors, increasing both DNA binding and transcriptional function on their respective response elements. This gene lies within the major histocompatibility complex (MHC) class II region on chromosome 6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

RXRB links:

SLC39A7 (HGNC:4927): (solute carrier family 39 member 7) The protein encoded by this gene transports zinc from the Golgi and endoplasmic reticulum to the cytoplasm. This transport may be important for activation of tyrosine kinases, some of which could be involved in cancer progression. Therefore, modulation of the encoded protein could be useful as a therapeutic agent against cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

SLC39A7 Gene-Disease associations (from GenCC):

agammaglobulinemia 9, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
agammaglobulinemia
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

SLC39A7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3102017).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021976.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RXRB	NM_021976.5	MANE Select	c.190G>A	p.Glu64Lys	missense	Exon 1 of 10	NP_068811.1	Q5STP9
RXRB	NM_001270401.2		c.190G>A	p.Glu64Lys	missense	Exon 1 of 10	NP_001257330.1	A0A0S2Z570
RXRB	NM_001291989.2		c.16+480G>A		intron	N/A	NP_001278918.1	A0A0G2JKR7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RXRB	ENST00000374680.4	TSL:1 MANE Select	c.190G>A	p.Glu64Lys	missense	Exon 1 of 10	ENSP00000363812.3	P28702-1
RXRB	ENST00000374685.8	TSL:1	c.190G>A	p.Glu64Lys	missense	Exon 1 of 10	ENSP00000363817.4	P28702-3
RXRB	ENST00000865272.1		c.190G>A	p.Glu64Lys	missense	Exon 1 of 10	ENSP00000535331.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

225446

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.18

M_CAP

Pathogenic

0.58

MetaRNN

Benign

0.31

MetaSVM

Uncertain

0.028

MutationAssessor

Benign

0.0

PhyloP100

3.3

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.14

REVEL

Uncertain

0.32

Sift

Uncertain

0.011

Sift4G

Benign

0.34

Polyphen

0.88

Vest4

0.43

MutPred

0.24

Gain of ubiquitination at E64 (P = 0.0014)

MVP

0.68

MPC

0.51

ClinPred

0.75

GERP RS

5.0

PromoterAI

0.00060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.24

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over