14-103715927-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024071.4(ZFYVE21):​c.86C>T​(p.Ala29Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000629 in 1,431,082 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 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000039 ( 0 hom. )

Consequence

ZFYVE21
NM_024071.4 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19
Variant links:
Genes affected
ZFYVE21 (HGNC:20760): (zinc finger FYVE-type containing 21) Predicted to enable metal ion binding activity. Predicted to be located in endosome and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38347828).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFYVE21NM_024071.4 linkc.86C>T p.Ala29Val missense_variant Exon 1 of 7 ENST00000311141.7 NP_076976.1 Q9BQ24-1
ZFYVE21NM_001198953.2 linkc.86C>T p.Ala29Val missense_variant Exon 1 of 8 NP_001185882.1 Q9BQ24-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFYVE21ENST00000311141.7 linkc.86C>T p.Ala29Val missense_variant Exon 1 of 7 1 NM_024071.4 ENSP00000310543.2 Q9BQ24-1

Frequencies

GnomAD3 genomes
AF:
0.0000264
AC:
4
AN:
151242
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000967
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
GnomAD4 exome
AF:
0.00000391
AC:
5
AN:
1279840
Hom.:
0
Cov.:
30
AF XY:
0.00000475
AC XY:
3
AN XY:
632106
show subpopulations
Gnomad4 AFR exome
AF:
0.000156
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.85e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000264
AC:
4
AN:
151242
Hom.:
0
Cov.:
33
AF XY:
0.0000271
AC XY:
2
AN XY:
73852
show subpopulations
Gnomad4 AFR
AF:
0.0000967
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:
0.0000340

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 03, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.86C>T (p.A29V) alteration is located in exon 1 (coding exon 1) of the ZFYVE21 gene. This alteration results from a C to T substitution at nucleotide position 86, causing the alanine (A) at amino acid position 29 to be replaced by a valine (V). 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
0.20
BayesDel_addAF
Benign
-0.052
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.023
.;T
Eigen
Uncertain
0.33
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Pathogenic
0.93
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.0
M;M
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-1.9
N;N
REVEL
Benign
0.17
Sift
Uncertain
0.015
D;D
Sift4G
Benign
0.091
T;T
Polyphen
0.98
D;D
Vest4
0.12
MVP
0.22
MPC
1.1
ClinPred
0.96
D
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.30
gMVP
0.34

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: rs749277267; hg19: chr14-104182264; API