chr16-70762591-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_018052.5(VAC14):c.1320G>A(p.Thr440Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000944 in 1,614,032 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0014 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00090 ( 10 hom. )
Consequence
VAC14
NM_018052.5 synonymous
NM_018052.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.86
Genes affected
VAC14 (HGNC:25507): (VAC14 component of PIKFYVE complex) This gene encodes a scaffold protein that is a component of the PIKfyve protein kinase complex. This complex is responsible for the synthesis of phosphatidylinositol 3,5-bisphosphate, an important component of cellular membranes, from phosphatidylinositol 3-phosphate. Mice lacking a functional copy of this gene exhibit severe neurodegeneration. Mutations in the human gene have been identified in patients with a childhood onset progressive neurological disorder characterized by impaired movement, dystonia, and striatal abnormalities. [provided by RefSeq, May 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=-0.59).
BP6
Variant 16-70762591-C-T is Benign according to our data. Variant chr16-70762591-C-T is described in ClinVar as [Benign]. Clinvar id is 784658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.86 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00139 (211/152276) while in subpopulation AMR AF= 0.0096 (147/15308). AF 95% confidence interval is 0.00834. There are 3 homozygotes in gnomad4. There are 95 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VAC14 | NM_018052.5 | c.1320G>A | p.Thr440Thr | synonymous_variant | 12/19 | ENST00000261776.10 | NP_060522.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VAC14 | ENST00000261776.10 | c.1320G>A | p.Thr440Thr | synonymous_variant | 12/19 | 1 | NM_018052.5 | ENSP00000261776.5 |
Frequencies
GnomAD3 genomes AF: 0.00139 AC: 212AN: 152156Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00371 AC: 932AN: 251082Hom.: 6 AF XY: 0.00293 AC XY: 398AN XY: 135718
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GnomAD4 exome AF: 0.000898 AC: 1313AN: 1461756Hom.: 10 Cov.: 30 AF XY: 0.000773 AC XY: 562AN XY: 727160
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GnomAD4 genome AF: 0.00139 AC: 211AN: 152276Hom.: 3 Cov.: 32 AF XY: 0.00128 AC XY: 95AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
VAC14-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 05, 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