rs17192170

Positions:

chr14-67790635-T-A

Variant summary

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

The NM_015346.4(ZFYVE26):c.2692A>T(p.Thr898Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,614,134 control chromosomes in the GnomAD database, including 11,951 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 878 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11073 hom. )

Consequence

ZFYVE26
NM_015346.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

ZFYVE26 (HGNC:20761): (zinc finger FYVE-type containing 26) This gene encodes a protein which contains a FYVE zinc finger binding domain. The presence of this domain is thought to target these proteins to membrane lipids through interaction with phospholipids in the membrane. Mutations in this gene are associated with autosomal recessive spastic paraplegia-15. [provided by RefSeq, Oct 2008]

ZFYVE26 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=0.0013203025).

BP6

Variant 14-67790635-T-A is Benign according to our data. Variant chr14-67790635-T-A is described in ClinVar as [Benign]. Clinvar id is 313909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-67790635-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFYVE26	NM_015346.4 linkuse as main transcript	c.2692A>T	p.Thr898Ser	missense_variant	15/42	ENST00000347230.9	NP_056161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFYVE26	ENST00000347230.9 linkuse as main transcript	c.2692A>T	p.Thr898Ser	missense_variant	15/42	1	NM_015346.4	ENSP00000251119	P1

Frequencies

GnomAD3 genomes

AF:

0.0896

AC:

13642

AN:

152182

Hom.:

879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0236

Gnomad AMI

AF:

0.261

Gnomad AMR

AF:

0.0788

Gnomad ASJ

AF:

0.0778

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0513

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.0840

GnomAD3 exomes

AF:

0.0914

AC:

22982

AN:

251464

Hom.:

1417

AF XY:

0.0942

AC XY:

12804

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0218

Gnomad AMR exome

AF:

0.0519

Gnomad ASJ exome

AF:

0.0811

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0566

Gnomad FIN exome

AF:

0.162

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.0981

GnomAD4 exome

AF:

0.118

AC:

172003

AN:

1461834

Hom.:

11073

Cov.:

AF XY:

0.116

AC XY:

84329

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.0538

Gnomad4 ASJ exome

AF:

0.0830

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0565

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.0896

AC:

13642

AN:

152300

Hom.:

878

Cov.:

AF XY:

0.0916

AC XY:

6820

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0235

Gnomad4 AMR

AF:

0.0787

Gnomad4 ASJ

AF:

0.0778

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0517

Gnomad4 FIN

AF:

0.173

Gnomad4 NFE

AF:

0.128

Gnomad4 OTH

AF:

0.0832

Alfa

AF:

0.115

Hom.:

833

Bravo

AF:

0.0793

TwinsUK

AF:

0.132

AC:

490

ALSPAC

AF:

0.131

AC:

503

ESP6500AA

AF:

0.0277

AC:

122

ESP6500EA

AF:

0.120

AC:

1032

ExAC

AF:

0.0903

AC:

10963

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.121

EpiControl

AF:

0.123

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 24, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Hereditary spastic paraplegia 15

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	- -

Spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 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

0.096

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0090

.;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.52

.;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.70

P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.044

Sift

Benign

0.38

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.041

.;B

Vest4

0.13

MutPred

0.14

Gain of glycosylation at T898 (P = 0.0402);Gain of glycosylation at T898 (P = 0.0402);

MPC

0.15

ClinPred

0.0027

GERP RS

2.4

gMVP

0.30

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