rs562237338
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_007059.4(KPTN):c.1167C>T(p.Gly389=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000305 in 1,607,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., cov: 26)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
KPTN
NM_007059.4 synonymous
NM_007059.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.721
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_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 19-47476547-G-A is Benign according to our data. Variant chr19-47476547-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 444477.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BP7
?
Synonymous conserved (PhyloP=-0.721 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KPTN | NM_007059.4 | c.1167C>T | p.Gly389= | synonymous_variant | 11/12 | ENST00000338134.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KPTN | ENST00000338134.8 | c.1167C>T | p.Gly389= | synonymous_variant | 11/12 | 1 | NM_007059.4 | P1 | |
ENST00000669287.1 | n.154G>A | non_coding_transcript_exon_variant | 2/2 | ||||||
KPTN | ENST00000594208.5 | c.*801C>T | 3_prime_UTR_variant, NMD_transcript_variant | 12/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000270 AC: 4AN: 148236Hom.: 0 Cov.: 26
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GnomAD3 exomes AF: 0.0000324 AC: 8AN: 246622Hom.: 0 AF XY: 0.0000521 AC XY: 7AN XY: 134254
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GnomAD4 exome AF: 0.0000308 AC: 45AN: 1459306Hom.: 0 Cov.: 31 AF XY: 0.0000482 AC XY: 35AN XY: 725518
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Macrocephaly-developmental delay syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2022 | This variant has not been reported in the literature in individuals affected with KPTN-related conditions. This sequence change affects codon 389 of the KPTN mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the KPTN protein. This variant is present in population databases (rs562237338, gnomAD 0.03%). ClinVar contains an entry for this variant (Variation ID: 444477). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | KPTN: BP4, BP7 - |
Computational scores
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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