Variant 4-2304502-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020972.3(ZFYVE28):c.1838C>T(p.Ala613Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,612,468 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00063 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

ZFYVE28
NM_020972.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009521484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZFYVE28	NM_020972.3 linkuse as main transcript	c.1838C>T	p.Ala613Val	missense_variant	8/13	ENST00000290974.7
ZFYVE28	NM_001172656.2 linkuse as main transcript	c.1748C>T	p.Ala583Val	missense_variant	7/12
ZFYVE28	NM_001172659.2 linkuse as main transcript	c.1628C>T	p.Ala543Val	missense_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFYVE28	ENST00000290974.7 linkuse as main transcript	c.1838C>T	p.Ala613Val	missense_variant	8/13	1	NM_020972.3	P2	Q9HCC9-1
	ENST00000510632.1 linkuse as main transcript	n.263-2389G>A		intron_variant, non_coding_transcript_variant		4
ZFYVE28	ENST00000511071.5 linkuse as main transcript	c.1748C>T	p.Ala583Val	missense_variant	7/12	5		A2	Q9HCC9-2
ZFYVE28	ENST00000515312.5 linkuse as main transcript	c.1628C>T	p.Ala543Val	missense_variant	8/13	2		A2	Q9HCC9-3

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000302

AC:

AN:

248392

Hom.:

AF XY:

0.000274

AC XY:

AN XY:

135014

show subpopulations

Gnomad AFR exome

AF:

0.00145

Gnomad AMR exome

AF:

0.000783

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000188

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000128

AC:

187

AN:

1460120

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

726226

show subpopulations

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000594

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000630

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.000793

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Oct 31, 2023

The c.1838C>T (p.A613V) alteration is located in exon 8 (coding exon 8) of the ZFYVE28 gene. This alteration results from a C to T substitution at nucleotide position 1838, causing the alanine (A) at amino acid position 613 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

0.087

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.014

T;.;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.0095

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.0

M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.042

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.91

P;B;.

Vest4

0.095

MVP

0.32

MPC

0.044

ClinPred

0.0072

GERP RS

1.6

Varity_R

0.047

gMVP

0.17

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