dbSNP rs112622970: ZFYVE16:p.Val43Ile (chr5-80436812-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001284236.3(ZFYVE16):c.127G>A(p.Val43Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,614,136 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 7 hom. )

Consequence

ZFYVE16
NM_001284236.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.06

Publications

2 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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057055354).

BP6

Variant 5-80436812-G-A is Benign according to our data. Variant chr5-80436812-G-A is described in ClinVar as Benign. ClinVar VariationId is 714256.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00527 (802/152306) while in subpopulation AFR AF = 0.0178 (740/41572). AF 95% confidence interval is 0.0167. There are 5 homozygotes in GnomAd4. There are 382 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

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.127G>A	p.Val43Ile	missense	Exon 4 of 19	NP_001271165.2	Q7Z3T8-1
ZFYVE16	NM_001105251.4		c.127G>A	p.Val43Ile	missense	Exon 4 of 19	NP_001098721.2	Q7Z3T8-1
ZFYVE16	NM_001349434.2		c.127G>A	p.Val43Ile	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.127G>A	p.Val43Ile	missense	Exon 4 of 19	ENSP00000426848.1	Q7Z3T8-1
ZFYVE16	ENST00000338008.9	TSL:1	c.127G>A	p.Val43Ile	missense	Exon 3 of 18	ENSP00000337159.5	Q7Z3T8-1
ZFYVE16	ENST00000510158.5	TSL:1	c.127G>A	p.Val43Ile	missense	Exon 4 of 19	ENSP00000423663.1	Q7Z3T8-1

Frequencies

GnomAD3 genomes

AF:

0.00524

AC:

797

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

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:

0.0000588

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00138

AC:

347

AN:

251218

AF XY:

0.00109

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000969

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000561

AC:

820

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000494

AC XY:

359

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0188

AC:

628

AN:

33478

American (AMR)

AF:

0.00119

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

1111984

Other (OTH)

AF:

0.00131

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

145

193

241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00527

AC:

802

AN:

152306

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

382

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0178

AC:

740

AN:

41572

American (AMR)

AF:

0.00288

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68034

Other (OTH)

AF:

0.00664

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00117

Hom.:

Bravo

AF:

0.00589

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00162

AC:

197

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

0.11

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0057

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

1.1

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.050

REVEL

Benign

0.070

Sift

Benign

0.17

Sift4G

Benign

0.51

Polyphen

0.52

Vest4

0.12

MVP

0.57

MPC

0.26

ClinPred

0.041

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.021

gMVP

0.026

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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