Variant rs1554047435 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_001284236.3(ZFYVE16):c.3442G>T(p.Asp1148Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZFYVE16
NM_001284236.3 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 9.86

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:

ZFYVE16 (HGNC:):

ZFYVE16 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 5-80451544-G-T is Pathogenic according to our data. Variant chr5-80451544-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 545111.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-80451544-G-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE16	NM_001284236.3 linkuse as main transcript	c.3442G>T	p.Asp1148Tyr	missense_variant	11/19	ENST00000505560.5	NP_001271165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE16	ENST00000505560.5 linkuse as main transcript	c.3442G>T	p.Asp1148Tyr	missense_variant	11/19	1	NM_001284236.3	ENSP00000426848.1		Q7Z3T8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461608

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cerebral arteriovenous malformation

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital

Feb 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;T

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

.;.;D

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.47

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-6.0

D;D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.50

MutPred

0.34

Loss of disorder (P = 0.0238);Loss of disorder (P = 0.0238);Loss of disorder (P = 0.0238);

MVP

0.65

MPC

0.34

ClinPred

0.99

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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