rs1556016381
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001008537.3(NEXMIF):c.3011_3014del(p.Ser1004IlefsTer5) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. S1004S) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 22)
Consequence
NEXMIF
NM_001008537.3 frameshift
NM_001008537.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.85
Genes affected
NEXMIF (HGNC:29433): (neurite extension and migration factor) An inversion on the X chromosome which disrupts this gene and a G-protein coupled purinergic receptor gene located in the pseudoautosomal region of the X chromosome has been linked to X linked cognitive disability.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 26 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-74741542-ATTAC-A is Pathogenic according to our data. Variant chrX-74741542-ATTAC-A is described in ClinVar as [Pathogenic]. Clinvar id is 474068.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEXMIF | NM_001008537.3 | c.3011_3014del | p.Ser1004IlefsTer5 | frameshift_variant | 3/4 | ENST00000055682.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEXMIF | ENST00000055682.12 | c.3011_3014del | p.Ser1004IlefsTer5 | frameshift_variant | 3/4 | 1 | NM_001008537.3 | P1 | |
NEXMIF | ENST00000616200.2 | c.3011_3014del | p.Ser1004IlefsTer5 | frameshift_variant | 3/5 | 1 | P1 | ||
NEXMIF | ENST00000642681.2 | c.3011_3014del | p.Ser1004IlefsTer5 | frameshift_variant | 3/3 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 24, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in KIAA2022 are known to be pathogenic (PMID: 23615299). This variant has not been reported in the literature in individuals with KIAA2022-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser1004Ilefs*5) in the KIAA2022 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at