rs1556016352
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001008537.3(NEXMIF):c.3226del(p.Thr1076ProfsTer14) 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 (★). Synonymous variant affecting the same amino acid position (i.e. T1076T) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 23)
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 22 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-74741330-GT-G is Pathogenic according to our data. Variant chrX-74741330-GT-G is described in ClinVar as [Pathogenic]. Clinvar id is 541124.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.3226del | p.Thr1076ProfsTer14 | frameshift_variant | 3/4 | ENST00000055682.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEXMIF | ENST00000055682.12 | c.3226del | p.Thr1076ProfsTer14 | frameshift_variant | 3/4 | 1 | NM_001008537.3 | P1 | |
NEXMIF | ENST00000616200.2 | c.3226del | p.Thr1076ProfsTer14 | frameshift_variant | 3/5 | 1 | P1 | ||
NEXMIF | ENST00000642681.2 | c.3226del | p.Thr1076ProfsTer14 | frameshift_variant | 3/3 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
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 | Feb 10, 2020 | This sequence change creates a premature translational stop signal (p.Thr1076Profs*14) in the KIAA2022 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KIAA2022-related conditions. ClinVar contains an entry for this variant (Variation ID: 541124). Loss-of-function variants in KIAA2022 are known to be pathogenic (PMID: 23615299). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
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Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at