GeneBe

rs10882993

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385875.1(ZFYVE27):​c.413G>C​(p.Gly138Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G138V) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Consequence

ZFYVE27
NM_001385875.1 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38

Publications

40 publications found
Variant links:
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]
ZFYVE27 Gene-Disease associations (from GenCC):
  • hereditary spastic paraplegia 33
    Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.073657274).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385875.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ZFYVE27
NM_001385875.1
MANE Select
c.413G>Cp.Gly138Ala
missense
Exon 4 of 13NP_001372804.1
ZFYVE27
NM_001385876.1
c.452G>Cp.Gly151Ala
missense
Exon 5 of 13NP_001372805.1
ZFYVE27
NM_001002261.4
c.413G>Cp.Gly138Ala
missense
Exon 4 of 13NP_001002261.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ZFYVE27
ENST00000684270.1
MANE Select
c.413G>Cp.Gly138Ala
missense
Exon 4 of 13ENSP00000506975.1
ZFYVE27
ENST00000393677.8
TSL:1
c.413G>Cp.Gly138Ala
missense
Exon 4 of 13ENSP00000377282.3
ZFYVE27
ENST00000423811.3
TSL:5
c.413G>Cp.Gly138Ala
missense
Exon 4 of 13ENSP00000409594.2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
84
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
19
DANN
Benign
0.89
DEOGEN2
Benign
0.0058
T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.59
D
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.074
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PhyloP100
2.4
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
1.3
N
REVEL
Benign
0.10
Sift
Uncertain
0.019
D
Sift4G
Uncertain
0.0080
D
Polyphen
0.0
B
Vest4
0.14
MutPred
0.16
Gain of helix (P = 0.0199)
MVP
0.095
ClinPred
0.47
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.12
gMVP
0.32
Mutation Taster
=98/2
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs10882993; hg19: chr10-99504630; API