NM_006917.5:c.403G>T

Variant names:

• chr1-165419909-C-A
• NM_006917.5:c.403G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006917.5(RXRG):​c.403G>T​(p.Val135Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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)
• Consequence: RXRG NM_006917.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46
• Publications: 0 publications found

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]

ENSG00000298458 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18479595).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006917.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRG	NM_006917.5	MANE Select	c.403G>T	p.Val135Phe	missense	Exon 3 of 10	NP_008848.1	P48443
	RXRG	NM_001256570.2		c.34G>T	p.Val12Phe	missense	Exon 4 of 11	NP_001243499.1	A0A087WZ88
	RXRG	NM_001256571.2		c.34G>T	p.Val12Phe	missense	Exon 2 of 9	NP_001243500.1	A0A087WZ88

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRG	ENST00000359842.10	TSL:1 MANE Select	c.403G>T	p.Val135Phe	missense	Exon 3 of 10	ENSP00000352900.5	P48443
	RXRG	ENST00000619224.1	TSL:1	c.34G>T	p.Val12Phe	missense	Exon 4 of 11	ENSP00000482458.1	A0A087WZ88
	RXRG	ENST00000885409.1		c.403G>T	p.Val135Phe	missense	Exon 3 of 10	ENSP00000555468.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.0067	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.066
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	0.37	N
PhyloP100		2.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.21
Sift	Benign	0.089	T
Sift4G	Benign	0.52	T
Polyphen		0.17	B
Vest4		0.27
MutPred		0.30		Loss of ubiquitination at K136 (P = 0.0863)
MVP		0.30
MPC		0.85
ClinPred		0.73	D
GERP RS		4.3
Varity_R		0.12
gMVP		0.52
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr1-165389146;