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GeneBe

1-165401297-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006917.5(RXRG):c.1358T>C(p.Met453Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RXRG
NM_006917.5 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.99
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.838

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RXRGNM_006917.5 linkuse as main transcriptc.1358T>C p.Met453Thr missense_variant 10/10 ENST00000359842.10
RXRGNM_001256570.2 linkuse as main transcriptc.989T>C p.Met330Thr missense_variant 11/11
RXRGNM_001256571.2 linkuse as main transcriptc.989T>C p.Met330Thr missense_variant 9/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RXRGENST00000359842.10 linkuse as main transcriptc.1358T>C p.Met453Thr missense_variant 10/101 NM_006917.5 P1
RXRGENST00000619224.1 linkuse as main transcriptc.989T>C p.Met330Thr missense_variant 11/111

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251462
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135900
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461810
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727222
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 GeneticsJul 25, 2023The c.1358T>C (p.M453T) alteration is located in exon 10 (coding exon 10) of the RXRG gene. This alteration results from a T to C substitution at nucleotide position 1358, causing the methionine (M) at amino acid position 453 to be replaced by a threonine (T). 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
0.88
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
Cadd
Uncertain
25
Dann
Uncertain
0.98
DEOGEN2
Uncertain
0.78
D;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.054
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Benign
-0.43
T
MutationAssessor
Benign
1.7
L;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-4.1
D;.
REVEL
Uncertain
0.63
Sift
Benign
0.033
D;.
Sift4G
Benign
0.13
T;T
Polyphen
0.84
P;.
Vest4
0.84
MutPred
0.47
Gain of catalytic residue at M453 (P = 0.0482);.;
MVP
0.53
MPC
1.6
ClinPred
0.97
D
GERP RS
4.6
Varity_R
0.63
gMVP
0.78

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: rs1306538888; hg19: chr1-165370534; API