chr14-72998065-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021260.4(ZFYVE1):ā€‹c.734A>Gā€‹(p.Asn245Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ZFYVE1
NM_021260.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25
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]

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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=0.19720843).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZFYVE1NM_021260.4 linkuse as main transcriptc.734A>G p.Asn245Ser missense_variant 3/12 ENST00000556143.6 NP_067083.1 Q9HBF4-1
ZFYVE1NM_001281734.2 linkuse as main transcriptc.734A>G p.Asn245Ser missense_variant 3/12 NP_001268663.1 Q9HBF4-3
ZFYVE1XM_047431481.1 linkuse as main transcriptc.734A>G p.Asn245Ser missense_variant 3/7 XP_047287437.1
ZFYVE1XM_047431482.1 linkuse as main transcriptc.-512A>G 5_prime_UTR_variant 3/12 XP_047287438.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZFYVE1ENST00000556143.6 linkuse as main transcriptc.734A>G p.Asn245Ser missense_variant 3/121 NM_021260.4 ENSP00000450742.1 Q9HBF4-1
ZFYVE1ENST00000318876.9 linkuse as main transcriptc.734A>G p.Asn245Ser missense_variant 3/121 ENSP00000326921.5 Q9HBF4-3
ZFYVE1ENST00000553891.5 linkuse as main transcriptc.734A>G p.Asn245Ser missense_variant 3/135 ENSP00000452442.1 G3V5N8

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461884
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsOct 08, 2024The c.734A>G (p.N245S) alteration is located in exon 3 (coding exon 2) of the ZFYVE1 gene. This alteration results from a A to G substitution at nucleotide position 734, causing the asparagine (N) at amino acid position 245 to be replaced by a serine (S). 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
0.12
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.041
T;.;T
Eigen
Benign
-0.012
Eigen_PC
Benign
0.11
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.20
T;T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
2.0
.;M;M
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-2.6
D;D;D
REVEL
Benign
0.11
Sift
Benign
0.069
T;T;T
Sift4G
Benign
0.15
T;T;T
Polyphen
0.31
B;.;B
Vest4
0.57
MutPred
0.35
Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);
MVP
0.13
MPC
0.30
ClinPred
0.84
D
GERP RS
4.7
Varity_R
0.18
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-73464773; API