chr8-2950230-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP3_Moderate
The NM_033225.6(CSMD1):c.10314+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,421,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_033225.6 splice_donor
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 |
---|---|---|---|---|---|---|---|
CSMD1 | NM_033225.6 | c.10314+1G>A | splice_donor_variant | ENST00000635120.2 | |||
LOC105377785 | NR_168443.1 | n.1172-58338C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSMD1 | ENST00000635120.2 | c.10314+1G>A | splice_donor_variant | 5 | NM_033225.6 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 7.04e-7 AC: 1AN: 1421378Hom.: 0 Cov.: 24 AF XY: 0.00000141 AC XY: 1AN XY: 709892
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
CSMD1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 31, 2023 | The CSMD1 c.10314+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. To date, limited evidence has been published on the role of variants predicted to interfere with splicing in CSMD1 in neurodevelopmental disorders. Therefore, although we suspect that this variant may possibly be pathogenic, at this time its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.