Variant 10-97743134-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001385875.1(ZFYVE27):c.238C>T(p.Leu80Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000335 in 1,614,188 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

ZFYVE27
NM_001385875.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.10

Variant links:

Genes affected

ZFYVE27 (HGNC:26559): (zinc finger FYVE-type containing 27) This gene encodes a protein with several transmembrane domains, a Rab11-binding domain and a lipid-binding FYVE finger domain. The encoded protein appears to promote neurite formation. A mutation in this gene has been reported to be associated with hereditary spastic paraplegia, however the pathogenicity of the mutation, which may simply represent a polymorphism, is unclear. [provided by RefSeq, Mar 2010]

ZFYVE27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0099259615).

BP6

Variant 10-97743134-C-T is Benign according to our data. Variant chr10-97743134-C-T is described in ClinVar as [Benign]. Clinvar id is 695222.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 284 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFYVE27	NM_001385875.1 linkuse as main transcript	c.238C>T	p.Leu80Phe	missense_variant	3/13	ENST00000684270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFYVE27	ENST00000684270.1 linkuse as main transcript	c.238C>T	p.Leu80Phe	missense_variant	3/13		NM_001385875.1	A1	Q5T4F4-1

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

284

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00664

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000429

AC:

108

AN:

251494

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00621

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000176

AC:

257

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00681

Gnomad4 AMR exome

AF:

0.000134

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:

0.00000180

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.00186

AC:

284

AN:

152300

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

130

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00662

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000263

Hom.:

Bravo

AF:

0.00194

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000478

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.014

T;.;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.0099

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

2.0

M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.2

N;.;N

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;.;D

Sift4G

Benign

0.11

T;T;T

Polyphen

0.99

D;D;P

Vest4

0.55

MVP

0.39

ClinPred

0.021

GERP RS

5.9

Varity_R

0.33

gMVP

0.45

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