rs112787369

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015346.4(ZFYVE26):c.3118T>A(p.Ser1040Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 1,614,158 control chromosomes in the GnomAD database, including 2,189 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 204 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1985 hom. )

Consequence

ZFYVE26
NM_015346.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.344

Publications

16 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), G2P, Orphanet, Myriad Women’s Health

ZFYVE26 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017139316).

BP6

Variant 14-67786135-A-T is Benign according to our data. Variant chr14-67786135-A-T is described in ClinVar as Benign. ClinVar VariationId is 130778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015346.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFYVE26	NM_015346.4	MANE Select	c.3118T>A	p.Ser1040Thr	missense	Exon 17 of 42	NP_056161.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFYVE26	ENST00000347230.9	TSL:1 MANE Select	c.3118T>A	p.Ser1040Thr	missense	Exon 17 of 42	ENSP00000251119.5	Q68DK2-1
ZFYVE26	ENST00000555452.1	TSL:1	c.3118T>A	p.Ser1040Thr	missense	Exon 17 of 35	ENSP00000450603.1	G3V2D8
ZFYVE26	ENST00000554523.5	TSL:1	n.3255T>A		non_coding_transcript_exon	Exon 17 of 41

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5985

AN:

152172

Hom.:

204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00934

Gnomad AMI

AF:

0.00989

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0114

Gnomad FIN

AF:

0.0306

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0497

Gnomad OTH

AF:

0.0445

GnomAD2 exomes

AF:

0.0494

AC:

12416

AN:

251448

AF XY:

0.0445

show subpopulations

Gnomad AFR exome

AF:

0.00849

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.00774

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0308

Gnomad NFE exome

AF:

0.0475

Gnomad OTH exome

AF:

0.0420

GnomAD4 exome

AF:

0.0458

AC:

66978

AN:

1461868

Hom.:

1985

Cov.:

AF XY:

0.0445

AC XY:

32382

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00726

AC:

243

AN:

33480

American (AMR)

AF:

0.152

AC:

6812

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

211

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0120

AC:

1038

AN:

86258

European-Finnish (FIN)

AF:

0.0344

AC:

1840

AN:

53418

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0489

AC:

54370

AN:

1111988

Other (OTH)

AF:

0.0396

AC:

2394

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

3892

7783

11675

15566

19458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1982

3964

5946

7928

9910

<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:

0.0393

AC:

5986

AN:

152290

Hom.:

204

Cov.:

AF XY:

0.0396

AC XY:

2952

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00931

AC:

387

AN:

41570

American (AMR)

AF:

0.112

AC:

1711

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0114

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0306

AC:

325

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0497

AC:

3379

AN:

68028

Other (OTH)

AF:

0.0441

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

294

589

883

1178

1472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0451

Hom.:

166

Bravo

AF:

0.0435

TwinsUK

AF:

0.0485

AC:

180

ALSPAC

AF:

0.0441

AC:

170

ESP6500AA

AF:

0.00999

AC:

ESP6500EA

AF:

0.0420

AC:

361

ExAC

AF:

0.0444

AC:

5385

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0452

EpiControl

AF:

0.0404

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia 15 (4)

not specified (4)

Hereditary spastic paraplegia (1)

not provided (1)

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.015

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

PhyloP100

0.34

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.75

REVEL

Benign

0.016

Sift

Benign

0.21

Sift4G

Benign

0.41

Polyphen

0.15

Vest4

0.31

MPC

0.17

ClinPred

0.0033

GERP RS

-0.57

gMVP

0.12

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over