chr19-47475538-GGCTGTGCTGTGGGGAACAAGAGAATGAGGGGGATGGAGCTGAGGAAGA-G
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_007059.4(KPTN):c.1183-42_1188del variant causes a splice acceptor, coding sequence, intron change. The variant allele was found at a frequency of 0.00000657 in 152,208 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: 0.0000062 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KPTN
NM_007059.4 splice_acceptor, coding_sequence, intron
NM_007059.4 splice_acceptor, coding_sequence, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.39
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 Pathogenic. Variant got 10 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease,
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.1183-42_1188del | splice_acceptor_variant, coding_sequence_variant, intron_variant | 12/12 | ENST00000338134.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KPTN | ENST00000338134.8 | c.1183-42_1188del | splice_acceptor_variant, coding_sequence_variant, intron_variant | 12/12 | 1 | NM_007059.4 | P1 | ||
ENST00000669287.1 | n.69-917_69-870del | intron_variant, non_coding_transcript_variant | |||||||
KPTN | ENST00000600551.1 | n.74-42_79del | splice_acceptor_variant, non_coding_transcript_exon_variant, intron_variant | 2/2 | 5 | ||||
KPTN | ENST00000594208.5 | c.*817-42_*822del | splice_acceptor_variant, 3_prime_UTR_variant, intron_variant, NMD_transcript_variant | 13/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 31
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000616 AC: 9AN: 1460348Hom.: 0 AF XY: 0.00000413 AC XY: 3AN XY: 726462
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 03, 2021 | The c.1183-42_1188del48 alteration is located in between Intron 11 (E) and Exon 12 of the KPTN gene. This alteration consists of a deletion of 48 nucleotides between nucleotide positions c.1183-42 and c.1188-42 between Intron 11 (E) and Exon 12. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at