rs1556016529
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001008537.3(NEXMIF):c.2166_2168delinsAC(p.Phe722LeufsTer7) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 22)
Consequence
NEXMIF
NM_001008537.3 frameshift
NM_001008537.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.67
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 46 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-74742389-TTA-GT is Pathogenic according to our data. Variant chrX-74742389-TTA-GT is described in ClinVar as [Pathogenic]. Clinvar id is 474060.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.2166_2168delinsAC | p.Phe722LeufsTer7 | frameshift_variant | 3/4 | ENST00000055682.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEXMIF | ENST00000055682.12 | c.2166_2168delinsAC | p.Phe722LeufsTer7 | frameshift_variant | 3/4 | 1 | NM_001008537.3 | P1 | |
NEXMIF | ENST00000616200.2 | c.2166_2168delinsAC | p.Phe722LeufsTer7 | frameshift_variant | 3/5 | 1 | P1 | ||
NEXMIF | ENST00000642681.2 | c.2166_2168delinsAC | p.Phe722LeufsTer7 | 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
X-linked intellectual disability, Cantagrel type Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 27, 2017 | This sequence change deletes 3 nucleotides and inserts 2 nucleotides in exon 3 of the KIAA2022 mRNA (c.2166_2168delinsAC), causing a frameshift at codon 722. This creates a premature translational stop signal (p.Phe722Leufs*7) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in KIAA2022 are known to be pathogenic (PMID: 27358180, 23615299). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at