chr4-2304568-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020972.3(ZFYVE28):c.1772T>C(p.Ile591Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,460,330 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: not found (cov: 34)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
ZFYVE28
NM_020972.3 missense
NM_020972.3 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 3.68
Genes affected
ZFYVE28 (HGNC:29334): (zinc finger FYVE-type containing 28) Enables phosphatidylinositol-3-phosphate binding activity. Involved in negative regulation of epidermal growth factor-activated receptor activity. Located in cytosol and early endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.16219342).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFYVE28 | NM_020972.3 | c.1772T>C | p.Ile591Thr | missense_variant | 8/13 | ENST00000290974.7 | |
ZFYVE28 | NM_001172656.2 | c.1682T>C | p.Ile561Thr | missense_variant | 7/12 | ||
ZFYVE28 | NM_001172659.2 | c.1562T>C | p.Ile521Thr | missense_variant | 8/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFYVE28 | ENST00000290974.7 | c.1772T>C | p.Ile591Thr | missense_variant | 8/13 | 1 | NM_020972.3 | P2 | |
ENST00000510632.1 | n.263-2323A>G | intron_variant, non_coding_transcript_variant | 4 | ||||||
ZFYVE28 | ENST00000511071.5 | c.1682T>C | p.Ile561Thr | missense_variant | 7/12 | 5 | A2 | ||
ZFYVE28 | ENST00000515312.5 | c.1562T>C | p.Ile521Thr | missense_variant | 8/13 | 2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247904Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134840
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460330Hom.: 0 Cov.: 38 AF XY: 0.00000413 AC XY: 3AN XY: 726458
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
Bravo
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2023 | The c.1772T>C (p.I591T) alteration is located in exon 8 (coding exon 8) of the ZFYVE28 gene. This alteration results from a T to C substitution at nucleotide position 1772, causing the isoleucine (I) at amino acid position 591 to be replaced by a threonine (T). 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
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Pathogenic
D;D;D
Sift4G
Benign
T;T;T
Polyphen
P;B;.
Vest4
MutPred
Gain of loop (P = 0.0312);.;.;
MVP
MPC
ClinPred
T
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