NM_015346.4:c.2112T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015346.4(ZFYVE26):c.2112T>C(p.Pro704Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,613,782 control chromosomes in the GnomAD database, including 366,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 36069 hom., cov: 31)

Exomes 𝑓: 0.67 ( 330359 hom. )

Consequence

ZFYVE26
NM_015346.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0810

Publications

28 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 14-67798150-A-G is Benign according to our data. Variant chr14-67798150-A-G is described in ClinVar as Benign. ClinVar VariationId is 695138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.081 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE26	NM_015346.4 link	c.2112T>C	p.Pro704Pro	synonymous_variant	Exon 11 of 42	ENST00000347230.9	NP_056161.2	Q68DK2-1
ZFYVE26	XM_047431173.1 link	c.2112T>C	p.Pro704Pro	synonymous_variant	Exon 11 of 42		XP_047287129.1
ZFYVE26	XM_011536609.3 link	c.2112T>C	p.Pro704Pro	synonymous_variant	Exon 11 of 26		XP_011534911.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFYVE26	ENST00000347230.9 link	c.2112T>C	p.Pro704Pro	synonymous_variant	Exon 11 of 42	1	NM_015346.4	ENSP00000251119.5		Q68DK2-1

Frequencies

GnomAD3 genomes

AF:

0.685

AC:

103982

AN:

151892

Hom.:

36044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.684

Gnomad AMI

AF:

0.652

Gnomad AMR

AF:

0.746

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.977

Gnomad SAS

AF:

0.774

Gnomad FIN

AF:

0.721

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.678

GnomAD2 exomes

AF:

0.715

AC:

179736

AN:

251258

AF XY:

0.713

show subpopulations

Gnomad AFR exome

AF:

0.684

Gnomad AMR exome

AF:

0.803

Gnomad ASJ exome

AF:

0.569

Gnomad EAS exome

AF:

0.978

Gnomad FIN exome

AF:

0.717

Gnomad NFE exome

AF:

0.648

Gnomad OTH exome

AF:

0.673

GnomAD4 exome

AF:

0.668

AC:

977085

AN:

1461772

Hom.:

330359

Cov.:

AF XY:

0.671

AC XY:

487842

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.680

AC:

22769

AN:

33480

American (AMR)

AF:

0.793

AC:

35472

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.578

AC:

15115

AN:

26132

East Asian (EAS)

AF:

0.976

AC:

38731

AN:

39698

South Asian (SAS)

AF:

0.779

AC:

67156

AN:

86254

European-Finnish (FIN)

AF:

0.716

AC:

38247

AN:

53404

Middle Eastern (MID)

AF:

0.642

AC:

3701

AN:

5768

European-Non Finnish (NFE)

AF:

0.643

AC:

715178

AN:

1111922

Other (OTH)

AF:

0.674

AC:

40716

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

20406

40812

61217

81623

102029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18926

37852

56778

75704

94630

<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:

0.685

AC:

104055

AN:

152010

Hom.:

36069

Cov.:

AF XY:

0.693

AC XY:

51461

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.683

AC:

28312

AN:

41432

American (AMR)

AF:

0.747

AC:

11401

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1958

AN:

3470

East Asian (EAS)

AF:

0.977

AC:

5065

AN:

5184

South Asian (SAS)

AF:

0.773

AC:

3720

AN:

4812

European-Finnish (FIN)

AF:

0.721

AC:

7629

AN:

10576

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.644

AC:

43779

AN:

67952

Other (OTH)

AF:

0.682

AC:

1440

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1645

3291

4936

6582

8227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<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:

0.655

Hom.:

134450

Bravo

AF:

0.686

Asia WGS

AF:

0.848

AC:

2948

AN:

3478

EpiCase

AF:

0.634

EpiControl

AF:

0.639

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Spastic paraplegia

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.73

(source)

DANN

Benign

0.42

PhyloP100

0.081

Mutation Taster

=100/0

polymorphism (auto)

(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