rs761799563
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP3_Moderate
The NM_021930.6(RINT1):c.2067+6_2067+9del variant causes a splice donor, coding sequence change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,542 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_021930.6 splice_donor, coding_sequence
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RINT1 | NM_021930.6 | c.2067+6_2067+9del | splice_donor_variant, coding_sequence_variant | 13/15 | ENST00000257700.7 | ||
EFCAB10 | NM_001355526.2 | c.*-12_*-9del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000480514.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RINT1 | ENST00000257700.7 | c.2067+6_2067+9del | splice_donor_variant, coding_sequence_variant | 13/15 | 1 | NM_021930.6 | P1 | ||
EFCAB10 | ENST00000480514.6 | c.*-12_*-9del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001355526.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000518 AC: 13AN: 251136Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135768
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461356Hom.: 0 AF XY: 0.0000206 AC XY: 15AN XY: 726956
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 23, 2022 | This sequence change falls in intron 13 of the RINT1 gene. It does not directly change the encoded amino acid sequence of the RINT1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs761799563, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RINT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 410784). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at