14-72997835-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021260.4(ZFYVE1):​c.964G>A​(p.Val322Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 1,598,416 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 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ZFYVE1
NM_021260.4 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1525402).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFYVE1NM_021260.4 linkc.964G>A p.Val322Met missense_variant Exon 3 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.964G>A p.Val322Met missense_variant Exon 3 of 12 1 NM_021260.4 ENSP00000450742.1 Q9HBF4-1
ZFYVE1ENST00000318876.9 linkc.964G>A p.Val322Met missense_variant Exon 3 of 12 1 ENSP00000326921.5 Q9HBF4-3
ZFYVE1ENST00000553891.5 linkc.964G>A p.Val322Met missense_variant Exon 3 of 13 5 ENSP00000452442.1 G3V5N8

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152126
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248058
Hom.:
0
AF XY:
0.00000747
AC XY:
1
AN XY:
133932
show subpopulations
Gnomad AFR exome
AF:
0.0000616
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000111
AC:
16
AN:
1446172
Hom.:
0
Cov.:
31
AF XY:
0.00000838
AC XY:
6
AN XY:
716026
show subpopulations
Gnomad4 AFR exome
AF:
0.000211
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000546
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152244
Hom.:
0
Cov.:
31
AF XY:
0.0000134
AC XY:
1
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
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
Mar 10, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.964G>A (p.V322M) alteration is located in exon 3 (coding exon 2) of the ZFYVE1 gene. This alteration results from a G to A substitution at nucleotide position 964, causing the valine (V) at amino acid position 322 to be replaced by a methionine (M). 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
0.13
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T;.;T
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.0
.;M;M
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
0.75
N;N;N
REVEL
Benign
0.089
Sift
Benign
0.078
T;T;T
Sift4G
Benign
0.13
T;T;T
Polyphen
0.57
P;.;P
Vest4
0.44
MVP
0.27
MPC
0.32
ClinPred
0.27
T
GERP RS
4.9
Varity_R
0.085
gMVP
0.65

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: rs193245467; hg19: chr14-73464543; API