chr19-47476545-A-ACGCCCTTCAGGGAGACCACGGCAAGCTCCTGCAGCCCATC
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_007059.4(KPTN):c.1168_1169insGATGGGCTGCAGGAGCTTGCCGTGGTCTCCCTGAAGGGCG(p.Val390GlyfsTer56) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 26)
Consequence
KPTN
NM_007059.4 frameshift
NM_007059.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.54
Genes affected
KPTN (HGNC:6404): (kaptin, actin binding protein) This gene encodes a filamentous-actin-associated protein, which is involved in actin dynamics and plays an important role in neuromorphogenesis. This protein is part of the KICSTOR protein complex that localizes to lysosomes. Mutations in this gene result in an autosomal recessive form of intellectual disability. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 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. Fraction of 0.109 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KPTN | NM_007059.4 | c.1168_1169insGATGGGCTGCAGGAGCTTGCCGTGGTCTCCCTGAAGGGCG | p.Val390GlyfsTer56 | frameshift_variant | 11/12 | ENST00000338134.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KPTN | ENST00000338134.8 | c.1168_1169insGATGGGCTGCAGGAGCTTGCCGTGGTCTCCCTGAAGGGCG | p.Val390GlyfsTer56 | frameshift_variant | 11/12 | 1 | NM_007059.4 | P1 | |
ENST00000669287.1 | n.154_193dup | non_coding_transcript_exon_variant | 2/2 | ||||||
KPTN | ENST00000594208.5 | c.*802_*803insGATGGGCTGCAGGAGCTTGCCGTGGTCTCCCTGAAGGGCG | 3_prime_UTR_variant, NMD_transcript_variant | 12/13 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 26
GnomAD3 genomes
?
Cov.:
26
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 26
GnomAD4 genome
?
Cov.:
26
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Macrocephaly-developmental delay syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Aug 30, 2022 | This variant was identified as homozygous._x000D_ Criteria applied: PVS1_MOD, PM2_SUP - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.