14-72993318-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021260.4(ZFYVE1):​c.1028G>A​(p.Arg343Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZFYVE1
NM_021260.4 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08
Variant links:
Genes affected
ZFYVE1 (HGNC:13180): (zinc finger FYVE-type containing 1) The FYVE domain mediates the recruitment of proteins involved in membrane trafficking and cell signaling to phosphatidylinositol 3-phosphate-containing membranes. This protein contains two zinc-binding FYVE domains in tandem and is reported to localize to the Golgi apparatus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFYVE1NM_021260.4 linkc.1028G>A p.Arg343Gln missense_variant Exon 4 of 12 ENST00000556143.6 NP_067083.1 Q9HBF4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFYVE1ENST00000556143.6 linkc.1028G>A p.Arg343Gln missense_variant Exon 4 of 12 1 NM_021260.4 ENSP00000450742.1 Q9HBF4-1
ZFYVE1ENST00000318876.9 linkc.1028G>A p.Arg343Gln missense_variant Exon 4 of 12 1 ENSP00000326921.5 Q9HBF4-3
ZFYVE1ENST00000553891.5 linkc.1028G>A p.Arg343Gln missense_variant Exon 4 of 13 5 ENSP00000452442.1 G3V5N8

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251416
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135896
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461826
Hom.:
0
Cov.:
34
AF XY:
0.00000413
AC XY:
3
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
28
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 23, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1028G>A (p.R343Q) alteration is located in exon 4 (coding exon 3) of the ZFYVE1 gene. This alteration results from a G to A substitution at nucleotide position 1028, causing the arginine (R) at amino acid position 343 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Uncertain
0.091
D
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.13
T;.;T
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.040
D
MetaRNN
Uncertain
0.60
D;D;D
MetaSVM
Uncertain
-0.18
T
MutationAssessor
Uncertain
2.6
.;M;M
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-3.0
D;D;D
REVEL
Uncertain
0.33
Sift
Uncertain
0.0070
D;D;D
Sift4G
Uncertain
0.020
D;D;D
Polyphen
0.98
D;.;P
Vest4
0.69
MVP
0.55
MPC
0.63
ClinPred
0.96
D
GERP RS
5.5
Varity_R
0.50
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs754283630; hg19: chr14-73460026; COSMIC: COSV100606565; API