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GeneBe

1-165419957-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006917.5(RXRG):c.355C>A(p.Pro119Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RXRG
NM_006917.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.11739123).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RXRGNM_006917.5 linkuse as main transcriptc.355C>A p.Pro119Thr missense_variant 3/10 ENST00000359842.10
RXRGNM_001256570.2 linkuse as main transcriptc.-15C>A 5_prime_UTR_variant 4/11
RXRGNM_001256571.2 linkuse as main transcriptc.-15C>A 5_prime_UTR_variant 2/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RXRGENST00000359842.10 linkuse as main transcriptc.355C>A p.Pro119Thr missense_variant 3/101 NM_006917.5 P1
RXRGENST00000619224.1 linkuse as main transcriptc.-15C>A 5_prime_UTR_variant 4/111
RXRGENST00000470566.1 linkuse as main transcriptn.280C>A non_coding_transcript_exon_variant 2/53

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1461090
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
726838
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:
0.0000144
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 GeneticsJul 09, 2021The c.355C>A (p.P119T) alteration is located in exon 3 (coding exon 3) of the RXRG gene. This alteration results from a C to A substitution at nucleotide position 355, causing the proline (P) at amino acid position 119 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
Benign
0.072
BayesDel_addAF
Benign
-0.042
T
BayesDel_noAF
Benign
-0.30
Cadd
Benign
22
Dann
Benign
0.88
DEOGEN2
Benign
0.31
T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.18
N
REVEL
Benign
0.18
Sift
Benign
0.22
T
Sift4G
Benign
0.34
T
Polyphen
0.10
B
Vest4
0.16
MutPred
0.26
Loss of disorder (P = 0.0648);
MVP
0.38
MPC
0.060
ClinPred
0.39
T
GERP RS
3.3
Varity_R
0.067
gMVP
0.36

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: chr1-165389194; API