chr19-47475422-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_007059.4(KPTN):c.1305C>T(p.Ala435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,612,344 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00031 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000097 ( 0 hom. )
Consequence
KPTN
NM_007059.4 synonymous
NM_007059.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.44
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 -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 19-47475422-G-A is Benign according to our data. Variant chr19-47475422-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 715187.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.43 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KPTN | NM_007059.4 | c.1305C>T | p.Ala435= | synonymous_variant | 12/12 | ENST00000338134.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KPTN | ENST00000338134.8 | c.1305C>T | p.Ala435= | synonymous_variant | 12/12 | 1 | NM_007059.4 | P1 | |
ENST00000669287.1 | n.69-1040G>A | intron_variant, non_coding_transcript_variant | |||||||
KPTN | ENST00000600551.1 | n.196C>T | non_coding_transcript_exon_variant | 2/2 | 5 | ||||
KPTN | ENST00000594208.5 | c.*939C>T | 3_prime_UTR_variant, NMD_transcript_variant | 13/13 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000309 AC: 47AN: 152196Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000198 AC: 49AN: 247492Hom.: 0 AF XY: 0.000201 AC XY: 27AN XY: 134440
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GnomAD4 exome AF: 0.0000966 AC: 141AN: 1460148Hom.: 0 Cov.: 31 AF XY: 0.000102 AC XY: 74AN XY: 726338
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GnomAD4 genome ? AF: 0.000309 AC: 47AN: 152196Hom.: 0 Cov.: 31 AF XY: 0.000430 AC XY: 32AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Macrocephaly-developmental delay syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 06, 2022 | - - |
Computational scores
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Name
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Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at