6-33199345-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_021976.5(RXRB):c.307C>T(p.Pro103Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000030 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RXRB NM_021976.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, RXRB
• BP4: Computational evidence support a benign effect (MetaRNN=0.11719927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RXRB	NM_021976.5	c.307C>T	p.Pro103Ser	missense_variant	2/10	ENST00000374680.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RXRB	ENST00000374680.4	c.307C>T	p.Pro103Ser	missense_variant	2/10	1	NM_021976.5	P4
RXRB	ENST00000374685.8	c.307C>T	p.Pro103Ser	missense_variant	2/10	1		A1
RXRB	ENST00000483281.5	c.236-881C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000301 AC: 3 AN: 998210 Hom.: 0 Cov.: 19 AF XY: 0.00000424 AC XY: 2 AN XY: 472154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000129

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: 0.00000118

Gnomad4 OTH exome AF: 0.0000260

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2023

The c.307C>T (p.P103S) alteration is located in exon 2 (coding exon 2) of the RXRB gene. This alteration results from a C to T substitution at nucleotide position 307, causing the proline (P) at amino acid position 103 to be replaced by a serine (S). 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	0.068
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
Cadd	Benign	20
Dann	Benign	0.73
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.75
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.26	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.13	T;T
Sift4G	Uncertain	0.060	T;T
Polyphen		0.075	.;B
Vest4		0.25
MutPred		0.40		Gain of phosphorylation at P103 (P = 8e-04);Gain of phosphorylation at P103 (P = 8e-04);
MVP		0.65
MPC		0.46
ClinPred		0.085	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-33167122;