rs17108378

Positions:

chr10-97743140-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001385875.1(ZFYVE27):c.244G>A(p.Val82Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,614,168 control chromosomes in the GnomAD database, including 900 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 0.029 ( 73 hom., cov: 32)

Exomes 𝑓: 0.031 ( 827 hom. )

Consequence

ZFYVE27
NM_001385875.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.14

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020341873).

BP6

Variant 10-97743140-G-A is Benign according to our data. Variant chr10-97743140-G-A is described in ClinVar as [Benign]. Clinvar id is 130785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-97743140-G-A is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFYVE27	NM_001385875.1 linkuse as main transcript	c.244G>A	p.Val82Ile	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.244G>A	p.Val82Ile	missense_variant	3/13		NM_001385875.1	A1	Q5T4F4-1

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

4483

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0287

Gnomad ASJ

AF:

0.0476

Gnomad EAS

AF:

0.0359

Gnomad SAS

AF:

0.0522

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0292

Gnomad OTH

AF:

0.0302

GnomAD3 exomes

AF:

0.0321

AC:

8063

AN:

251492

Hom.:

162

AF XY:

0.0340

AC XY:

4616

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0305

Gnomad AMR exome

AF:

0.0166

Gnomad ASJ exome

AF:

0.0434

Gnomad EAS exome

AF:

0.0379

Gnomad SAS exome

AF:

0.0551

Gnomad FIN exome

AF:

0.0188

Gnomad NFE exome

AF:

0.0314

Gnomad OTH exome

AF:

0.0309

GnomAD4 exome

AF:

0.0308

AC:

45083

AN:

1461858

Hom.:

827

Cov.:

AF XY:

0.0318

AC XY:

23162

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0295

Gnomad4 AMR exome

AF:

0.0177

Gnomad4 ASJ exome

AF:

0.0430

Gnomad4 EAS exome

AF:

0.0391

Gnomad4 SAS exome

AF:

0.0558

Gnomad4 FIN exome

AF:

0.0195

Gnomad4 NFE exome

AF:

0.0294

Gnomad4 OTH exome

AF:

0.0321

GnomAD4 genome

AF:

0.0295

AC:

4486

AN:

152310

Hom.:

Cov.:

AF XY:

0.0294

AC XY:

2189

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0295

Gnomad4 AMR

AF:

0.0286

Gnomad4 ASJ

AF:

0.0476

Gnomad4 EAS

AF:

0.0358

Gnomad4 SAS

AF:

0.0527

Gnomad4 FIN

AF:

0.0153

Gnomad4 NFE

AF:

0.0292

Gnomad4 OTH

AF:

0.0299

Alfa

AF:

0.0310

Hom.:

167

Bravo

AF:

0.0301

TwinsUK

AF:

0.0283

AC:

105

ALSPAC

AF:

0.0285

AC:

110

ESP6500AA

AF:

0.0327

AC:

144

ESP6500EA

AF:

0.0315

AC:

271

ExAC

AF:

0.0334

AC:

4055

Asia WGS

AF:

0.0370

AC:

128

AN:

3478

EpiCase

AF:

0.0302

EpiControl

AF:

0.0308

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 33

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.046

DANN

Benign

0.78

DEOGEN2

Benign

0.0040

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.51

T;T;T

MetaRNN

Benign

0.0020

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.5

N;N;N

MutationTaster

Benign

1.0

D;D;D;D;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.060

N;.;N

REVEL

Benign

0.018

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.064

ClinPred

0.0029

GERP RS

-7.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.018

gMVP

0.085

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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