Genetic Variant ZFYVE16:p.Gly297Ser (chr5-80437574-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001284236.3(ZFYVE16):c.889G>A(p.Gly297Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ZFYVE16
NM_001284236.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Publications

0 publications found

Variant links:

Genes affected

ZFYVE16 (HGNC:20756): (zinc finger FYVE-type containing 16) This gene encodes an endosomal protein that belongs to the FYVE zinc finger family of proteins. The encoded protein is thought to regulate membrane trafficking in the endosome. This protein functions as a scaffold protein in the transforming growth factor-beta signaling pathway and is involved in positive and negative feedback regulation of the bone morphogenetic protein signaling pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ZFYVE16 links:

FAM151B-DT (HGNC:55578): (FAM151B divergent transcript)

FAM151B-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013861328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFYVE16	NM_001284236.3	MANE Select	c.889G>A	p.Gly297Ser	missense	Exon 4 of 19	NP_001271165.2	Q7Z3T8-1
ZFYVE16	NM_001105251.4		c.889G>A	p.Gly297Ser	missense	Exon 4 of 19	NP_001098721.2	Q7Z3T8-1
ZFYVE16	NM_001349434.2		c.889G>A	p.Gly297Ser	missense	Exon 4 of 19	NP_001336363.2	Q7Z3T8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFYVE16	ENST00000505560.5	TSL:1 MANE Select	c.889G>A	p.Gly297Ser	missense	Exon 4 of 19	ENSP00000426848.1	Q7Z3T8-1
ZFYVE16	ENST00000338008.9	TSL:1	c.889G>A	p.Gly297Ser	missense	Exon 3 of 18	ENSP00000337159.5	Q7Z3T8-1
ZFYVE16	ENST00000510158.5	TSL:1	c.889G>A	p.Gly297Ser	missense	Exon 4 of 19	ENSP00000423663.1	Q7Z3T8-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000184

AC:

AN:

250190

AF XY:

0.000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000986

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00110

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111962

Other (OTH)

AF:

0.0000331

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41392

American (AMR)

AF:

0.000131

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.000148

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.8

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.72

M_CAP

Benign

0.0072

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

1.3

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.77

REVEL

Benign

0.023

Sift

Benign

0.31

Sift4G

Benign

0.16

Polyphen

0.025

Vest4

0.098

MutPred

0.21

Loss of sheet (P = 0.0357)

MVP

0.38

MPC

0.049

ClinPred

0.014

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.060

gMVP

0.061

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over