2-96761085-T-TGCTGTGGGC
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_020184.4(CNNM4):c.91_99dup(p.Trp31_Leu33dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00000407 in 1,473,248 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000038 ( 0 hom. )
Consequence
CNNM4
NM_020184.4 inframe_insertion
NM_020184.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.36
Genes affected
CNNM4 (HGNC:105): (cyclin and CBS domain divalent metal cation transport mediator 4) This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play a role in metal ion transport. Mutations in this gene are associated with Jalili syndrome which consists of cone-rod dystrophy and amelogenesis imperfecta. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_020184.4.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CNNM4 | NM_020184.4 | c.91_99dup | p.Trp31_Leu33dup | inframe_insertion | 1/7 | ENST00000377075.3 | NP_064569.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CNNM4 | ENST00000377075.3 | c.91_99dup | p.Trp31_Leu33dup | inframe_insertion | 1/7 | 1 | NM_020184.4 | ENSP00000366275 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000662 AC: 1AN: 151150Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000378 AC: 5AN: 1322098Hom.: 0 Cov.: 31 AF XY: 0.00000155 AC XY: 1AN XY: 645910
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GnomAD4 genome AF: 0.00000662 AC: 1AN: 151150Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 73788
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 17, 2022 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 999867). This variant has not been reported in the literature in individuals affected with CNNM4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant, c.91_99dup, results in the insertion of 3 amino acid(s) of the CNNM4 protein (p.Trp31_Leu33dup), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at