6-33200451-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_021976.5(RXRB):āc.26T>Cā(p.Phe9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00028 in 1,593,190 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 (ā ).
Frequency
Genomes: š 0.00020 ( 0 hom., cov: 32)
Exomes š: 0.00029 ( 0 hom. )
Consequence
RXRB
NM_021976.5 missense
NM_021976.5 missense
Scores
3
8
7
Clinical Significance
Conservation
PhyloP100: 2.15
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.23382723).
BS2
High AC in GnomAd4 at 31 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RXRB | NM_021976.5 | c.26T>C | p.Phe9Ser | missense_variant | 1/10 | ENST00000374680.4 | NP_068811.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RXRB | ENST00000374680.4 | c.26T>C | p.Phe9Ser | missense_variant | 1/10 | 1 | NM_021976.5 | ENSP00000363812 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000133 AC: 28AN: 210244Hom.: 0 AF XY: 0.000139 AC XY: 16AN XY: 114958
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GnomAD4 exome AF: 0.000288 AC: 415AN: 1440906Hom.: 0 Cov.: 31 AF XY: 0.000278 AC XY: 199AN XY: 715148
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GnomAD4 genome AF: 0.000204 AC: 31AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74478
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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 | Aug 01, 2022 | The c.26T>C (p.F9S) alteration is located in exon 1 (coding exon 1) of the RXRB gene. This alteration results from a T to C substitution at nucleotide position 26, causing the phenylalanine (F) at amino acid position 9 to be replaced by a serine (S). 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
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
0.91
.;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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