rs140128583
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_015346.4(ZFYVE26):āc.624T>Cā(p.Asp208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 1,614,168 control chromosomes in the GnomAD database, including 1 homozygotes. 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: š 0.00031 ( 0 hom., cov: 32)
Exomes š: 0.00047 ( 1 hom. )
Consequence
ZFYVE26
NM_015346.4 synonymous
NM_015346.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.457
Genes affected
ZFYVE26 (HGNC:20761): (zinc finger FYVE-type containing 26) This gene encodes a protein which contains a FYVE zinc finger binding domain. The presence of this domain is thought to target these proteins to membrane lipids through interaction with phospholipids in the membrane. Mutations in this gene are associated with autosomal recessive spastic paraplegia-15. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 14-67807660-A-G is Benign according to our data. Variant chr14-67807660-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 413792.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=-0.457 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.624T>C | p.Asp208= | synonymous_variant | 5/42 | ENST00000347230.9 | |
ZFYVE26 | XM_047431173.1 | c.624T>C | p.Asp208= | synonymous_variant | 5/42 | ||
ZFYVE26 | XM_011536609.3 | c.624T>C | p.Asp208= | synonymous_variant | 5/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.624T>C | p.Asp208= | synonymous_variant | 5/42 | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000309 AC: 47AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000558 AC: 140AN: 251098Hom.: 0 AF XY: 0.000582 AC XY: 79AN XY: 135818
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GnomAD4 exome AF: 0.000465 AC: 680AN: 1461834Hom.: 1 Cov.: 32 AF XY: 0.000455 AC XY: 331AN XY: 727214
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GnomAD4 genome ? AF: 0.000309 AC: 47AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74500
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2022 | ZFYVE26: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 30, 2018 | - - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 01, 2018 | - - |
ZFYVE26-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 18, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
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