chr6-33199227-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_021976.5(RXRB):c.425C>T(p.Ser142Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,208,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000073 ( 0 hom., cov: 28)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
RXRB
NM_021976.5 missense
NM_021976.5 missense
Scores
1
11
5
Clinical Significance
Conservation
PhyloP100: 7.41
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, RXRB
BP4
?
Computational evidence support a benign effect (MetaRNN=0.351915).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RXRB | NM_021976.5 | c.425C>T | p.Ser142Phe | missense_variant | 2/10 | ENST00000374680.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RXRB | ENST00000374680.4 | c.425C>T | p.Ser142Phe | missense_variant | 2/10 | 1 | NM_021976.5 | P4 | |
RXRB | ENST00000374685.8 | c.425C>T | p.Ser142Phe | missense_variant | 2/10 | 1 | A1 | ||
RXRB | ENST00000483281.5 | c.236-763C>T | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000728 AC: 1AN: 137388Hom.: 0 Cov.: 28
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GnomAD4 exome AF: 0.0000121 AC: 13AN: 1071282Hom.: 0 Cov.: 25 AF XY: 0.00000787 AC XY: 4AN XY: 507996
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GnomAD4 genome ? AF: 0.00000728 AC: 1AN: 137388Hom.: 0 Cov.: 28 AF XY: 0.0000152 AC XY: 1AN XY: 65730
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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 submitter | clinical testing | Ambry Genetics | Sep 12, 2023 | The c.425C>T (p.S142F) alteration is located in exon 2 (coding exon 2) of the RXRB gene. This alteration results from a C to T substitution at nucleotide position 425, causing the serine (S) at amino acid position 142 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
0.98
.;D
Vest4
MutPred
Loss of phosphorylation at S142 (P = 0.0042);Loss of phosphorylation at S142 (P = 0.0042);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at