ENST00000619224.1:c.-217C>G

Variant names:

• chr1-165428805-G-C
• ENST00000619224.1:c.-217C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000619224.1(RXRG):​c.-217C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-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: 33)
• Consequence: RXRG ENST00000619224.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.106

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRG	NM_006917.5	c.211C>G	p.Arg71Gly	missense_variant	Exon 2 of 10	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.-217C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11		NP_001243499.1
RXRG	NM_001256570.2	c.-217C>G		5_prime_UTR_variant	Exon 2 of 11		NP_001243499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000619224.1	c.-217C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11	1		ENSP00000482458.1
RXRG	ENST00000359842.10	c.211C>G	p.Arg71Gly	missense_variant	Exon 2 of 10	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.-217C>G		5_prime_UTR_variant	Exon 2 of 11	1		ENSP00000482458.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.211C>G (p.R71G) alteration is located in exon 2 (coding exon 2) of the RXRG gene. This alteration results from a C to G substitution at nucleotide position 211, causing the arginine (R) at amino acid position 71 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.33	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.2	L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.080	N
REVEL	Uncertain	0.46
Sift	Benign	0.26	T
Sift4G	Benign	0.41	T
Polyphen		0.48	P
Vest4		0.73
MutPred		0.33		Gain of catalytic residue at V72 (P = 0.0211);
MVP		0.63
MPC		0.39
ClinPred		0.58	D
GERP RS		-2.9
Varity_R		0.11
gMVP		0.44

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: chr1-165398042; COSMIC: COSV100717262; COSMIC: COSV100717262;