chr19-47480979-C-T
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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.504G>A(p.Pro168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 1,601,960 control chromosomes in the GnomAD database, including 648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.021 ( 74 hom., cov: 31)
Exomes 𝑓: 0.025 ( 574 hom. )
Consequence
KPTN
NM_007059.4 synonymous
NM_007059.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.74
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=-0.76).
BP6
Variant 19-47480979-C-T is Benign according to our data. Variant chr19-47480979-C-T is described in ClinVar as [Benign]. Clinvar id is 474857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.74 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0214 (3257/152246) while in subpopulation NFE AF= 0.0296 (2012/68016). AF 95% confidence interval is 0.0285. There are 74 homozygotes in gnomad4. There are 1694 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 74 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KPTN | NM_007059.4 | c.504G>A | p.Pro168= | synonymous_variant | 5/12 | ENST00000338134.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KPTN | ENST00000338134.8 | c.504G>A | p.Pro168= | synonymous_variant | 5/12 | 1 | NM_007059.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0214 AC: 3260AN: 152128Hom.: 74 Cov.: 31
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GnomAD3 exomes AF: 0.0218 AC: 4900AN: 225106Hom.: 101 AF XY: 0.0211 AC XY: 2585AN XY: 122268
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GnomAD4 exome AF: 0.0251 AC: 36401AN: 1449714Hom.: 574 Cov.: 32 AF XY: 0.0245 AC XY: 17634AN XY: 720186
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GnomAD4 genome AF: 0.0214 AC: 3257AN: 152246Hom.: 74 Cov.: 31 AF XY: 0.0228 AC XY: 1694AN XY: 74438
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ClinVar
Significance: Benign
Submissions summary: Benign:3
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 29, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2021 | - - |
KPTN-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 08, 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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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