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GeneBe

1-165411030-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_006917.5(RXRG):c.702G>A(p.Met234Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RXRG
NM_006917.5 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.66
Variant links:
Genes affected
RXRG (HGNC:10479): (retinoid X receptor gamma) This gene encodes a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the antiproliferative effects of retinoic acid (RA). This receptor forms dimers with the retinoic acid, thyroid hormone, and vitamin D receptors, increasing both DNA binding and transcriptional function on their respective response elements. This gene is expressed at significantly lower levels in non-small cell lung cancer cells. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jun 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RXRGNM_006917.5 linkuse as main transcriptc.702G>A p.Met234Ile missense_variant 5/10 ENST00000359842.10
RXRGNM_001256570.2 linkuse as main transcriptc.333G>A p.Met111Ile missense_variant 6/11
RXRGNM_001256571.2 linkuse as main transcriptc.333G>A p.Met111Ile missense_variant 4/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RXRGENST00000359842.10 linkuse as main transcriptc.702G>A p.Met234Ile missense_variant 5/101 NM_006917.5 P1
RXRGENST00000619224.1 linkuse as main transcriptc.333G>A p.Met111Ile missense_variant 6/111
RXRGENST00000470566.1 linkuse as main transcriptn.627G>A non_coding_transcript_exon_variant 4/53

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251198
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135758
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461844
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727224
show subpopulations
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.00000824
AC:
1

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 GeneticsMar 20, 2023The c.702G>A (p.M234I) alteration is located in exon 5 (coding exon 5) of the RXRG gene. This alteration results from a G to A substitution at nucleotide position 702, causing the methionine (M) at amino acid position 234 to be replaced by an isoleucine (I). 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
Pathogenic
0.87
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
Cadd
Uncertain
25
Dann
Uncertain
0.99
DEOGEN2
Uncertain
0.75
D;.
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Benign
0.079
D
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Uncertain
0.060
D
MutationAssessor
Uncertain
2.1
M;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-3.2
D;.
REVEL
Uncertain
0.44
Sift
Benign
0.073
T;.
Sift4G
Benign
0.13
T;T
Polyphen
0.96
D;.
Vest4
0.59
MutPred
0.21
Loss of loop (P = 0.1258);.;
MVP
0.62
MPC
1.6
ClinPred
0.97
D
GERP RS
4.7
Varity_R
0.64
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs757312135; hg19: chr1-165380267; API