rs397514545
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_014254.3(RXYLT1):βc.1064_1091delβ(p.Asp355ValfsTer33) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. D355D) has been classified as Likely benign.
Frequency
Consequence
NM_014254.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RXYLT1 | NM_014254.3 | c.1064_1091del | p.Asp355ValfsTer33 | frameshift_variant | 6/6 | ENST00000261234.11 | |
RXYLT1-AS1 | NR_126167.1 | non_coding_transcript_exon_variant | 4/4 | ||||
RXYLT1 | NM_001278237.2 | c.284_311del | p.Asp95ValfsTer33 | frameshift_variant | 6/6 | ||
RXYLT1 | XM_047428078.1 | c.755_782del | p.Asp252ValfsTer33 | frameshift_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RXYLT1 | ENST00000261234.11 | c.1064_1091del | p.Asp355ValfsTer33 | frameshift_variant | 6/6 | 1 | NM_014254.3 | P1 | |
RXYLT1-AS1 | ENST00000546214.1 | non_coding_transcript_exon_variant | 4/4 | 4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251290Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135820
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461824Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 727206
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 27, 2020 | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | This sequence change creates a premature translational stop signal (p.Asp355Valfs*33) in the RXYLT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 89 amino acid(s) of the RXYLT1 protein. This variant is present in population databases (rs397514545, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with cobblestone lissencephaly (PMID: 23217329). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 39606). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 07, 2012 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at