rs776927068

Variant names:

• chr1-165406827-G-A
• rs776927068
• NM_006917.5:c.1229C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-165406827-G-A
• chr1-165406827-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_006917.5(RXRG):​c.1229C>T​(p.Pro410Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,196 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. P410Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: RXRG NM_006917.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.68

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 Likely_benign. Variant got -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRG	NM_006917.5	c.1229C>T	p.Pro410Leu	missense_variant	Exon 9 of 10	ENST00000359842.10	NP_008848.1
RXRG	NM_001256570.2	c.860C>T	p.Pro287Leu	missense_variant	Exon 10 of 11		NP_001243499.1
RXRG	NM_001256571.2	c.860C>T	p.Pro287Leu	missense_variant	Exon 8 of 9		NP_001243500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRG	ENST00000359842.10	c.1229C>T	p.Pro410Leu	missense_variant	Exon 9 of 10	1	NM_006917.5	ENSP00000352900.5
RXRG	ENST00000619224.1	c.860C>T	p.Pro287Leu	missense_variant	Exon 10 of 11	1		ENSP00000482458.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251116 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135684

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461196 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.97	D;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Uncertain	0.56	D
MutationAssessor	Pathogenic	4.0	H;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-8.3	D;.
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;.
Vest4		0.68
MVP		0.77
MPC		2.5
ClinPred		1.0	D
GERP RS		4.2
Varity_R		0.87
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs776927068; hg19: chr1-165376064; COSMIC: COSV63233063; COSMIC: COSV63233063;