Variant 15-40807842-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001077268.2(ZFYVE19):c.253G>A(p.Val85Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000716 in 1,535,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

ZFYVE19
NM_001077268.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.35

Variant links:

Genes affected

ZFYVE19 (HGNC:20758): (zinc finger FYVE-type containing 19) Enables phosphatidylinositol-3-phosphate binding activity. Involved in abscission; mitotic cytokinesis checkpoint signaling; and negative regulation of cytokinesis. Located in centrosome; cleavage furrow; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ZFYVE19 links:

Genome browser will be placed here

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=0.15830919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE19	NM_001077268.2 linkuse as main transcript	c.253G>A	p.Val85Ile	missense_variant	1/11	ENST00000355341.8	NP_001070736.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE19	ENST00000355341.8 linkuse as main transcript	c.253G>A	p.Val85Ile	missense_variant	1/11	1	NM_001077268.2	ENSP00000347498	P2	Q96K21-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

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:

0.0000216

AC:

AN:

185558

Hom.:

AF XY:

0.0000301

AC XY:

AN XY:

99648

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000243

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:

0.00000578

AC:

AN:

1383528

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

682286

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000153

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000249

AC:

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

Feb 28, 2023

The c.253G>A (p.V85I) alteration is located in exon 1 (coding exon 1) of the ZFYVE19 gene. This alteration results from a G to A substitution at nucleotide position 253, causing the valine (V) at amino acid position 85 to be replaced by an isoleucine (I). 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

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;T;.;.

Eigen

Benign

-0.068

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.8

.;L;L;.

MutationTaster

Benign

1.0

D;D;N;N;N

PROVEAN

Benign

-0.43

N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.27

T;T;T;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.15, 0.041

.;B;B;.

Vest4

0.13

MutPred

0.50

.;Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);.;

MVP

0.32

MPC

0.37

ClinPred

0.48

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.10

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over