chr6-33195674-G-C

Position:

• chr6-33195674-G-C

Variant summary

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

The NM_021976.5(RXRB):​c.1152C>G​(p.Phe384Leu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RXRB NM_021976.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99

Genes affected

RXRB (HGNC:10478): (retinoid X receptor beta) This gene encodes a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the effects of retinoic acid (RA). The encoded protein forms homodimers with the retinoic acid, thyroid hormone, and vitamin D receptors, increasing both DNA binding and transcriptional function on their respective response elements. This gene lies within the major histocompatibility complex (MHC) class II region on chromosome 6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

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, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RXRB	NM_021976.5	c.1152C>G	p.Phe384Leu	missense_variant	7/10	ENST00000374680.4	NP_068811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RXRB	ENST00000374680.4	c.1152C>G	p.Phe384Leu	missense_variant	7/10	1	NM_021976.5	ENSP00000363812.3
RXRB	ENST00000374685.8	c.1152C>G	p.Phe384Leu	missense_variant	7/10	1		ENSP00000363817.4
RXRB	ENST00000483281.5	n.*664C>G		non_coding_transcript_exon_variant	6/9	5		ENSP00000431369.1
RXRB	ENST00000483281.5	n.*664C>G		3_prime_UTR_variant	6/9	5		ENSP00000431369.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152010 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 56

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 152010 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74224

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	.;D
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.98	L;L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.6	D;D
REVEL	Uncertain	0.49
Sift	Benign	0.043	D;D
Sift4G	Benign	0.19	T;T
Polyphen		1.0	.;D
Vest4		0.84
MutPred		0.49		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.85
MPC		1.6
ClinPred		0.94	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.91

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: rs6531; hg19: chr6-33163451;