rs376664624
Positions:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001385875.1(ZFYVE27):c.800C>T(p.Thr267Met) variant causes a missense change. The variant allele was found at a frequency of 0.000115 in 1,613,938 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 Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
ZFYVE27
NM_001385875.1 missense
NM_001385875.1 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 3.63
Genes affected
ZFYVE27 (HGNC:26559): (zinc finger FYVE-type containing 27) This gene encodes a protein with several transmembrane domains, a Rab11-binding domain and a lipid-binding FYVE finger domain. The encoded protein appears to promote neurite formation. A mutation in this gene has been reported to be associated with hereditary spastic paraplegia, however the pathogenicity of the mutation, which may simply represent a polymorphism, is unclear. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18441951).
BS2
?
High AC in GnomAd4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE27 | NM_001385875.1 | c.800C>T | p.Thr267Met | missense_variant | 7/13 | ENST00000684270.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE27 | ENST00000684270.1 | c.800C>T | p.Thr267Met | missense_variant | 7/13 | NM_001385875.1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152216Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250922Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135720
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GnomAD4 exome AF: 0.000119 AC: 174AN: 1461722Hom.: 0 Cov.: 55 AF XY: 0.000121 AC XY: 88AN XY: 727170
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GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74368
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 05, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 28, 2023 | The c.800C>T (p.T267M) alteration is located in exon 6 (coding exon 6) of the ZFYVE27 gene. This alteration results from a C to T substitution at nucleotide position 800, causing the threonine (T) at amino acid position 267 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;T;D;D;T;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;.;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;.;D
Sift4G
Benign
T;T;D;T;T;D;T
Polyphen
0.99, 1.0, 1.0, 1.0
.;.;.;D;D;D;D
Vest4
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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