rs1416940954

Variant names:

• chr1-165410774-C-G
• NM_006917.5:c.841G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-165410774-C-G
• chr1-165410774-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006917.5(RXRG):​c.841G>C​(p.Val281Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V281I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RXRG NM_006917.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.66

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRG	NM_006917.5	c.841G>C	p.Val281Leu	missense_variant	Exon 6 of 10	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.472G>C	p.Val158Leu	missense_variant	Exon 7 of 11		NP_001243499.1
RXRG	NM_001256571.2	c.472G>C	p.Val158Leu	missense_variant	Exon 5 of 9		NP_001243500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000359842.10	c.841G>C	p.Val281Leu	missense_variant	Exon 6 of 10	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.472G>C	p.Val158Leu	missense_variant	Exon 7 of 11	1		ENSP00000482458.1
RXRG	ENST00000470566.1	n.766G>C		non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461818 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727196

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.95	D;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.47	D
MutationAssessor	Uncertain	2.9	M;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.8	D;.
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;.
Vest4		0.84
MutPred		0.79		Gain of catalytic residue at V281 (P = 0.0133);.;
MVP		0.85
MPC		1.5
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.91
gMVP		0.75

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: chr1-165380011;