rs17419023

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001385875.1(ZFYVE27):c.126C>T(p.Leu42Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00712 in 1,613,914 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 49 hom. )

Consequence

ZFYVE27
NM_001385875.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.392

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 33
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ZFYVE27 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 10-97738603-C-T is Benign according to our data. Variant chr10-97738603-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 238205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.392 with no splicing effect.

BS2

High AC in GnomAd4 at 768 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE27	NM_001385875.1 link	c.126C>T	p.Leu42Leu	synonymous_variant	Exon 2 of 13	ENST00000684270.1	NP_001372804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE27	ENST00000684270.1 link	c.126C>T	p.Leu42Leu	synonymous_variant	Exon 2 of 13		NM_001385875.1	ENSP00000506975.1

Frequencies

GnomAD3 genomes

AF:

0.00507

AC:

770

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00688

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00123

Gnomad MID

AF:

0.0132

Gnomad NFE

AF:

0.00840

Gnomad OTH

AF:

0.00482

GnomAD2 exomes

AF:

0.00489

AC:

1229

AN:

251496

AF XY:

0.00532

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00515

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.00708

Gnomad OTH exome

AF:

0.00831

GnomAD4 exome

AF:

0.00734

AC:

10723

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00724

AC XY:

5264

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00105

AC:

AN:

33480

American (AMR)

AF:

0.00521

AC:

233

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00435

AC:

375

AN:

86258

European-Finnish (FIN)

AF:

0.00176

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00832

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00853

AC:

9480

AN:

1112006

Other (OTH)

AF:

0.00727

AC:

439

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

640

1280

1920

2560

3200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.00505

AC:

768

AN:

152034

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

343

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

41442

American (AMR)

AF:

0.00687

AC:

105

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00248

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00123

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0141

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.00839

AC:

570

AN:

67944

Other (OTH)

AF:

0.00429

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

134

178

223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00652

Hom.:

Bravo

AF:

0.00501

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00921

EpiControl

AF:

0.00889

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 33

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:2

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZFYVE27: BP4, BP7, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Spastic paraplegia

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jun 25, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.7

(source)

DANN

Benign

0.88

PhyloP100

0.39

Mutation Taster

=100/0

polymorphism

(source)

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

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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