Variant chr4-2304313-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_020972.3(ZFYVE28):c.2027C>T(p.Ala676Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000765 in 1,594,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 36)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

ZFYVE28
NM_020972.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.59

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:

ENSG00000251148 (HGNC:):

ENSG00000251148 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04104227).

BP6

Variant 4-2304313-G-A is Benign according to our data. Variant chr4-2304313-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3473667.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE28	NM_020972.3 link	c.2027C>T	p.Ala676Val	missense_variant	8/13	ENST00000290974.7	NP_066023.2	Q9HCC9-1
ZFYVE28	NM_001172656.2 link	c.1937C>T	p.Ala646Val	missense_variant	7/12		NP_001166127.1	Q9HCC9-2
ZFYVE28	NM_001172659.2 link	c.1817C>T	p.Ala606Val	missense_variant	8/13		NP_001166130.1	Q9HCC9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZFYVE28	ENST00000290974.7 link	c.2027C>T	p.Ala676Val	missense_variant	8/13	1	NM_020972.3	ENSP00000290974.3	Q9HCC9-1
ZFYVE28	ENST00000511071.5 link	c.1937C>T	p.Ala646Val	missense_variant	7/12	5		ENSP00000425706.1	Q9HCC9-2
ZFYVE28	ENST00000515312.5 link	c.1817C>T	p.Ala606Val	missense_variant	8/13	2		ENSP00000426299.1	Q9HCC9-3
ENSG00000251148	ENST00000510632.1 link	n.263-2578G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000900

AC:

AN:

233320

Hom.:

AF XY:

0.0000860

AC XY:

AN XY:

127928

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.0000908

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000135

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000102

Gnomad OTH exome

AF:

0.000344

GnomAD4 exome

AF:

0.0000700

AC:

101

AN:

1442332

Hom.:

Cov.:

AF XY:

0.0000613

AC XY:

AN XY:

717548

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.0000694

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000106

Gnomad4 FIN exome

AF:

0.0000234

Gnomad4 NFE exome

AF:

0.0000605

Gnomad4 OTH exome

AF:

0.000284

GnomAD4 genome

AF:

0.000138

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000221

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000660

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.010

DANN

Benign

0.63

DEOGEN2

Benign

0.014

T;.;.

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.0079

LIST_S2

Benign

0.37

T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.041

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.043

Sift

Benign

0.11

T;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.012

MVP

0.27

MPC

0.044

ClinPred

0.032

GERP RS

-7.6

Varity_R

0.025

gMVP

0.20

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