6-33200424-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_021976.5(RXRB):ā€‹c.53A>Gā€‹(p.Gln18Arg) 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. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RXRB
NM_021976.5 missense

Scores

2
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30223453).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RXRBNM_021976.5 linkuse as main transcriptc.53A>G p.Gln18Arg missense_variant 1/10 ENST00000374680.4 NP_068811.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RXRBENST00000374680.4 linkuse as main transcriptc.53A>G p.Gln18Arg missense_variant 1/101 NM_021976.5 ENSP00000363812 P4P28702-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1432280
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
710136
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 24, 2024The c.53A>G (p.Q18R) alteration is located in exon 1 (coding exon 1) of the RXRB gene. This alteration results from a A to G substitution at nucleotide position 53, causing the glutamine (Q) at amino acid position 18 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.31
.;T
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Benign
0.27
N
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-0.34
T
MutationAssessor
Benign
0.69
N;N
MutationTaster
Benign
0.58
D;D;D;N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.18
N;N
REVEL
Uncertain
0.37
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.030
D;D
Polyphen
0.12
.;B
Vest4
0.35
MutPred
0.32
Gain of MoRF binding (P = 0.0087);Gain of MoRF binding (P = 0.0087);
MVP
0.75
MPC
0.49
ClinPred
0.61
D
GERP RS
4.5
Varity_R
0.24
gMVP
0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-33168201; API