2-96761084-CT-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020184.4(CNNM4):c.86del(p.Leu29ArgfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000227 in 1,318,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L29L) has been classified as Likely benign.
Frequency
Consequence
NM_020184.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNNM4 | NM_020184.4 | c.86del | p.Leu29ArgfsTer21 | frameshift_variant | 1/7 | ENST00000377075.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNNM4 | ENST00000377075.3 | c.86del | p.Leu29ArgfsTer21 | frameshift_variant | 1/7 | 1 | NM_020184.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000227 AC: 3AN: 1318812Hom.: 0 Cov.: 31 AF XY: 0.00000155 AC XY: 1AN XY: 644032
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2022 | This variant has not been reported in the literature in individuals affected with CNNM4-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu29Argfs*21) in the CNNM4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CNNM4 are known to be pathogenic (PMID: 19200525). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.