rs575306476
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001385875.1(ZFYVE27):āc.557A>Gā(p.Tyr186Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.000066 ( 0 hom., cov: 33)
Exomes š: 0.000030 ( 0 hom. )
Consequence
ZFYVE27
NM_001385875.1 missense
NM_001385875.1 missense
Scores
5
9
3
Clinical Significance
Conservation
PhyloP100: 6.36
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE27 | NM_001385875.1 | c.557A>G | p.Tyr186Cys | missense_variant | 6/13 | ENST00000684270.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE27 | ENST00000684270.1 | c.557A>G | p.Tyr186Cys | missense_variant | 6/13 | NM_001385875.1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152020Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
10
AN:
152020
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251486Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135918
GnomAD3 exomes
AF:
AC:
8
AN:
251486
Hom.:
AF XY:
AC XY:
3
AN XY:
135918
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461640Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727160
GnomAD4 exome
AF:
AC:
44
AN:
1461640
Hom.:
Cov.:
31
AF XY:
AC XY:
18
AN XY:
727160
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152138Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74368
GnomAD4 genome
?
AF:
AC:
10
AN:
152138
Hom.:
Cov.:
33
AF XY:
AC XY:
3
AN XY:
74368
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
4
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 15, 2022 | ClinVar contains an entry for this variant (Variation ID: 570689). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with ZFYVE27-related conditions. This variant is present in population databases (rs575306476, gnomAD 0.005%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 186 of the ZFYVE27 protein (p.Tyr186Cys). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;.;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D;.;D
Sift4G
Uncertain
D;D;D;D;D;D;D
Polyphen
1.0
.;.;.;D;D;D;D
Vest4
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at