Variant 4-2304568-A-G 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_020972.3(ZFYVE28):c.1772T>C(p.Ile591Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,460,330 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: not found (cov: 34)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ZFYVE28
NM_020972.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

Variant links:

Genes affected

ZFYVE28 (HGNC:29334): (zinc finger FYVE-type containing 28) Enables phosphatidylinositol-3-phosphate binding activity. Involved in negative regulation of epidermal growth factor-activated receptor activity. Located in cytosol and early endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ZFYVE28 links:

(HGNC:):

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=0.16219342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZFYVE28	NM_020972.3 linkuse as main transcript	c.1772T>C	p.Ile591Thr	missense_variant	8/13	ENST00000290974.7
ZFYVE28	NM_001172656.2 linkuse as main transcript	c.1682T>C	p.Ile561Thr	missense_variant	7/12
ZFYVE28	NM_001172659.2 linkuse as main transcript	c.1562T>C	p.Ile521Thr	missense_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFYVE28	ENST00000290974.7 linkuse as main transcript	c.1772T>C	p.Ile591Thr	missense_variant	8/13	1	NM_020972.3	P2	Q9HCC9-1
	ENST00000510632.1 linkuse as main transcript	n.263-2323A>G		intron_variant, non_coding_transcript_variant		4
ZFYVE28	ENST00000511071.5 linkuse as main transcript	c.1682T>C	p.Ile561Thr	missense_variant	7/12	5		A2	Q9HCC9-2
ZFYVE28	ENST00000515312.5 linkuse as main transcript	c.1562T>C	p.Ile521Thr	missense_variant	8/13	2		A2	Q9HCC9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247904

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134840

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

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:

0.00000548

AC:

AN:

1460330

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726458

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Nov 09, 2023

The c.1772T>C (p.I591T) alteration is located in exon 8 (coding exon 8) of the ZFYVE28 gene. This alteration results from a T to C substitution at nucleotide position 1772, causing the isoleucine (I) at amino acid position 591 to be replaced by a threonine (T). 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

0.090

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.041

T;.;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.82

T;T;T

M_CAP

Uncertain

0.089

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.6

M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.33

T;T;T

Polyphen

0.50

P;B;.

Vest4

0.18

MutPred

0.27

Gain of loop (P = 0.0312);.;.;

MVP

0.34

MPC

0.054

ClinPred

0.26

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.22

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.

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