rs1553624279
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_000965.5(RARB):c.409C>T(p.Arg137Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000965.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RARB | NM_000965.5 | c.409C>T | p.Arg137Ter | stop_gained | 3/8 | ENST00000330688.9 | |
LOC124909356 | XR_007095847.1 | n.903G>A | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RARB | ENST00000330688.9 | c.409C>T | p.Arg137Ter | stop_gained | 3/8 | 1 | NM_000965.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1458040Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725230
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Microphthalmia, syndromic 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing;provider interpretation | Geisinger Autism and Developmental Medicine Institute, Geisinger Health System | May 23, 2017 | This variant was identified in a 6 year old male with global developmental delay, autism spectrum disorder, pica, and atopic dermatitis. It is absent from the gnomAD database and is predicted to result in loss of protein function due to truncation or nonsense-mediated mRNA decay. It was inherited from a mother who has a history of learning difficulties in grade school. She completed 14 years of education. Neither the proband nor his mother have had ophthalmologic evaluations but there are no vision concerns. There were no additional variants identified in the RARB gene. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 10, 2017 | The R137X variant in the RARB gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R137X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret R137X as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at