ENST00000557366.5:n.2385delT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000557366.5(ZFYVE26):n.2385delT variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,613,816 control chromosomes in the GnomAD database, including 355 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 82 hom., cov: 32)

Exomes 𝑓: 0.014 ( 273 hom. )

Consequence

ZFYVE26
ENST00000557366.5 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.296

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 15
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, G2P

ZFYVE26 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 14-67797664-CA-C is Benign according to our data. Variant chr14-67797664-CA-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 313914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ZFYVE26	NM_015346.4 link	c.2332+7delT	splice_region_variant, intron_variant	Intron 12 of 41	ENST00000347230.9	NP_056161.2
ZFYVE26	XM_047431173.1 link	c.2332+7delT	splice_region_variant, intron_variant	Intron 12 of 41		XP_047287129.1
ZFYVE26	XM_011536609.3 link	c.2332+7delT	splice_region_variant, intron_variant	Intron 12 of 25		XP_011534911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE26	ENST00000347230.9 link	c.2332+7delT		splice_region_variant, intron_variant	Intron 12 of 41	1	NM_015346.4	ENSP00000251119.5

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3882

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0596

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00968

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0519

Gnomad SAS

AF:

0.0159

Gnomad FIN

AF:

0.00726

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0230

GnomAD2 exomes

AF:

0.0169

AC:

4231

AN:

251080

AF XY:

0.0157

show subpopulations

Gnomad AFR exome

AF:

0.0631

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.0514

Gnomad FIN exome

AF:

0.00579

Gnomad NFE exome

AF:

0.0123

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0145

AC:

21186

AN:

1461558

Hom.:

273

Cov.:

AF XY:

0.0144

AC XY:

10454

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.0582

AC:

1949

AN:

33478

American (AMR)

AF:

0.00537

AC:

240

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00111

AC:

AN:

26120

East Asian (EAS)

AF:

0.0606

AC:

2407

AN:

39694

South Asian (SAS)

AF:

0.0158

AC:

1365

AN:

86182

European-Finnish (FIN)

AF:

0.00723

AC:

386

AN:

53400

Middle Eastern (MID)

AF:

0.00936

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0124

AC:

13802

AN:

1111830

Other (OTH)

AF:

0.0158

AC:

954

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

1139

2277

3416

4554

5693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

594

1188

1782

2376

2970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0256

AC:

3896

AN:

152258

Hom.:

Cov.:

AF XY:

0.0251

AC XY:

1865

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0598

AC:

2483

AN:

41538

American (AMR)

AF:

0.00960

AC:

147

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.0522

AC:

270

AN:

5174

South Asian (SAS)

AF:

0.0162

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00726

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

778

AN:

68012

Other (OTH)

AF:

0.0227

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

190

381

571

762

952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00393

Hom.:

Bravo

AF:

0.0277

Asia WGS

AF:

0.0330

AC:

113

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.0115

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spastic paraplegia

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Nov 27, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Benign:1

Nov 11, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spastic Paraplegia, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Sep 30, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary spastic paraplegia 15

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.30

Mutation Taster

=84/16

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over