Variant 5-80437434-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001284236.3(ZFYVE16):c.749G>A(p.Arg250Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,602,334 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 71 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 42 hom. )

Consequence

ZFYVE16
NM_001284236.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.753

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010974705).

BP6

Variant 5-80437434-G-A is Benign according to our data. Variant chr5-80437434-G-A is described in ClinVar as [Benign]. Clinvar id is 768011.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFYVE16	NM_001284236.3 linkuse as main transcript	c.749G>A	p.Arg250Gln	missense_variant	4/19	ENST00000505560.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFYVE16	ENST00000505560.5 linkuse as main transcript	c.749G>A	p.Arg250Gln	missense_variant	4/19	1	NM_001284236.3	P1	Q7Z3T8-1
FAM151B-DT	ENST00000666568.1 linkuse as main transcript	n.259-22967C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

2602

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00426

AC:

1018

AN:

238974

Hom.:

AF XY:

0.00314

AC XY:

407

AN XY:

129684

show subpopulations

Gnomad AFR exome

AF:

0.0563

Gnomad AMR exome

AF:

0.00284

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00118

Gnomad SAS exome

AF:

0.0000691

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000824

Gnomad OTH exome

AF:

0.00368

GnomAD4 exome

AF:

0.00159

AC:

2299

AN:

1450174

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

979

AN XY:

720714

show subpopulations

Gnomad4 AFR exome

AF:

0.0553

Gnomad4 AMR exome

AF:

0.00415

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000556

Gnomad4 SAS exome

AF:

0.000106

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000343

Gnomad4 OTH exome

AF:

0.00392

GnomAD4 genome

AF:

0.0172

AC:

2619

AN:

152160

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1236

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0579

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00376

Hom.:

Bravo

AF:

0.0209

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0600

AC:

264

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00512

AC:

622

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.73

Cadd

Benign

Dann

Benign

0.081

DEOGEN2

Benign

0.00040

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0043

MetaRNN

Benign

0.0011

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.8

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.10

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.93

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.070

MVP

0.19

MPC

0.050

ClinPred

0.0013

GERP RS

5.1

Varity_R

0.029

gMVP

0.045

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

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