rs73940855
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_007059.4(KPTN):c.1056C>T(p.His352=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,612,904 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 43 hom., cov: 27)
Exomes 𝑓: 0.0017 ( 42 hom. )
Consequence
KPTN
NM_007059.4 synonymous
NM_007059.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.17
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 19-47476658-G-A is Benign according to our data. Variant chr19-47476658-G-A is described in ClinVar as [Benign]. Clinvar id is 474855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.17 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2134/151576) while in subpopulation AFR AF= 0.0485 (2005/41340). AF 95% confidence interval is 0.0467. There are 43 homozygotes in gnomad4. There are 1015 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 43 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KPTN | NM_007059.4 | c.1056C>T | p.His352= | synonymous_variant | 11/12 | ENST00000338134.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KPTN | ENST00000338134.8 | c.1056C>T | p.His352= | synonymous_variant | 11/12 | 1 | NM_007059.4 | P1 | |
ENST00000669287.1 | n.265G>A | non_coding_transcript_exon_variant | 2/2 | ||||||
KPTN | ENST00000594208.5 | c.*690C>T | 3_prime_UTR_variant, NMD_transcript_variant | 12/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0140 AC: 2122AN: 151456Hom.: 42 Cov.: 27
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GnomAD3 exomes AF: 0.00338 AC: 833AN: 246242Hom.: 15 AF XY: 0.00259 AC XY: 348AN XY: 134168
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GnomAD4 exome AF: 0.00170 AC: 2480AN: 1461328Hom.: 42 Cov.: 31 AF XY: 0.00150 AC XY: 1087AN XY: 726926
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GnomAD4 genome ? AF: 0.0141 AC: 2134AN: 151576Hom.: 43 Cov.: 27 AF XY: 0.0137 AC XY: 1015AN XY: 74038
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Macrocephaly-developmental delay syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2024 | - - |
KPTN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 15, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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