rs367857763
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015346.4(ZFYVE26):āc.6287T>Cā(p.Leu2096Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
ZFYVE26
NM_015346.4 missense
NM_015346.4 missense
Scores
3
13
Clinical Significance
Conservation
PhyloP100: 3.89
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.14556888).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE26 | NM_015346.4 | c.6287T>C | p.Leu2096Pro | missense_variant | 34/42 | ENST00000347230.9 | |
ZFYVE26 | XM_047431173.1 | c.6287T>C | p.Leu2096Pro | missense_variant | 34/42 | ||
ZFYVE26 | XM_047431174.1 | c.3962T>C | p.Leu1321Pro | missense_variant | 23/31 | ||
ZFYVE26 | XM_047431175.1 | c.3869T>C | p.Leu1290Pro | missense_variant | 23/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE26 | ENST00000347230.9 | c.6287T>C | p.Leu2096Pro | missense_variant | 34/42 | 1 | NM_015346.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251332Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135836
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727248
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
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32
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ESP6500AA
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 13, 2021 | This sequence change replaces leucine with proline at codon 2096 of the ZFYVE26 protein (p.Leu2096Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant has not been reported in the literature in individuals affected with ZFYVE26-related conditions. ClinVar contains an entry for this variant (Variation ID: 216692). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.12
.;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
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Calibrated prediction
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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