chr1-165419963-C-G

Variant names:

• chr1-165419963-C-G
• NM_006917.5:c.349G>C

Variant summary

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

The NM_006917.5(RXRG):​c.349G>C​(p.Gly117Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.27
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.349G>C	p.Gly117Arg	missense	Exon 3 of 10	NP_008848.1	P48443
	RXRG	NM_001256570.2		c.-21G>C		5_prime_UTR	Exon 4 of 11	NP_001243499.1	A0A087WZ88
	RXRG	NM_001256571.2		c.-21G>C		5_prime_UTR	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.349G>C	p.Gly117Arg	missense	Exon 3 of 10	ENSP00000352900.5	P48443
	RXRG	ENST00000619224.1	TSL:1	c.-21G>C		5_prime_UTR	Exon 4 of 11	ENSP00000482458.1	A0A087WZ88
	RXRG	ENST00000885409.1		c.349G>C	p.Gly117Arg	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	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.73	D
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.63
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.086	T
Polyphen		0.97	D
Vest4		0.67
MutPred		0.18		Loss of methylation at K113 (P = 0.1204)
MVP		0.64
MPC		0.30
ClinPred		0.94	D
GERP RS		4.2
Varity_R		0.19
gMVP		0.72
Mutation Taster		=74/26	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: chr1-165389200;