Variant 4-2274104-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020972.3(ZFYVE28):c.2164G>A(p.Gly722Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,622 control chromosomes in the GnomAD database, including 1 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 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000092 ( 1 hom. )

Consequence

ZFYVE28
NM_020972.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010648072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZFYVE28	NM_020972.3 linkuse as main transcript	c.2164G>A	p.Gly722Ser	missense_variant	9/13	ENST00000290974.7
ZFYVE28	NM_001172656.2 linkuse as main transcript	c.2074G>A	p.Gly692Ser	missense_variant	8/12
ZFYVE28	NM_001172659.2 linkuse as main transcript	c.1954G>A	p.Gly652Ser	missense_variant	9/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFYVE28	ENST00000290974.7 linkuse as main transcript	c.2164G>A	p.Gly722Ser	missense_variant	9/13	1	NM_020972.3	P2	Q9HCC9-1
ZFYVE28	ENST00000508471.5 linkuse as main transcript	c.79G>A	p.Gly27Ser	missense_variant	3/7	1		A2
ZFYVE28	ENST00000511071.5 linkuse as main transcript	c.2074G>A	p.Gly692Ser	missense_variant	8/12	5		A2	Q9HCC9-2
ZFYVE28	ENST00000515312.5 linkuse as main transcript	c.1954G>A	p.Gly652Ser	missense_variant	9/13	2		A2	Q9HCC9-3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000144

AC:

AN:

250698

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000924

AC:

135

AN:

1461320

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000381

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000189

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

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

Dec 21, 2023

The c.2164G>A (p.G722S) alteration is located in exon 9 (coding exon 9) of the ZFYVE28 gene. This alteration results from a G to A substitution at nucleotide position 2164, causing the glycine (G) at amino acid position 722 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

0.065

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0026

T;T;.;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.40

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

0.97

D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.072

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.65, 0.38

.;P;B;.

Vest4

0.12

MVP

0.13

MPC

0.053

ClinPred

0.058

GERP RS

2.5

Varity_R

0.065

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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