10-97743140-G-A

Variant names:

Variant summary

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

The NM_001385875.1(ZFYVE27):c.244G>A(p.Val82Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,614,168 control chromosomes in the GnomAD database, including 900 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 73 hom., cov: 32)

Exomes 𝑓: 0.031 ( 827 hom. )

Consequence

ZFYVE27
NM_001385875.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.14

Publications

19 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: ClinGen, Labcorp Genetics (formerly Invitae)

ZFYVE27 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=0.0020341873).

BP6

Variant 10-97743140-G-A is Benign according to our data. Variant chr10-97743140-G-A is described in ClinVar as Benign. ClinVar VariationId is 130785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385875.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFYVE27	NM_001385875.1	MANE Select	c.244G>A	p.Val82Ile	missense	Exon 3 of 13	NP_001372804.1	Q5T4F4-1
ZFYVE27	NM_001385876.1		c.244G>A	p.Val82Ile	missense	Exon 3 of 13	NP_001372805.1
ZFYVE27	NM_001002261.4		c.244G>A	p.Val82Ile	missense	Exon 3 of 13	NP_001002261.1	Q5T4F4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFYVE27	ENST00000684270.1	MANE Select	c.244G>A	p.Val82Ile	missense	Exon 3 of 13	ENSP00000506975.1	Q5T4F4-1
ZFYVE27	ENST00000393677.8	TSL:1	c.244G>A	p.Val82Ile	missense	Exon 3 of 13	ENSP00000377282.3	Q5T4F4-1
ZFYVE27	ENST00000423811.3	TSL:5	c.244G>A	p.Val82Ile	missense	Exon 3 of 13	ENSP00000409594.2	Q5T4F4-3

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

4483

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0287

Gnomad ASJ

AF:

0.0476

Gnomad EAS

AF:

0.0359

Gnomad SAS

AF:

0.0522

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0292

Gnomad OTH

AF:

0.0302

GnomAD2 exomes

AF:

0.0321

AC:

8063

AN:

251492

AF XY:

0.0340

show subpopulations

Gnomad AFR exome

AF:

0.0305

Gnomad AMR exome

AF:

0.0166

Gnomad ASJ exome

AF:

0.0434

Gnomad EAS exome

AF:

0.0379

Gnomad FIN exome

AF:

0.0188

Gnomad NFE exome

AF:

0.0314

Gnomad OTH exome

AF:

0.0309

GnomAD4 exome

AF:

0.0308

AC:

45083

AN:

1461858

Hom.:

827

Cov.:

AF XY:

0.0318

AC XY:

23162

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0295

AC:

987

AN:

33478

American (AMR)

AF:

0.0177

AC:

790

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0430

AC:

1124

AN:

26134

East Asian (EAS)

AF:

0.0391

AC:

1551

AN:

39700

South Asian (SAS)

AF:

0.0558

AC:

4810

AN:

86254

European-Finnish (FIN)

AF:

0.0195

AC:

1044

AN:

53420

Middle Eastern (MID)

AF:

0.0324

AC:

187

AN:

5768

European-Non Finnish (NFE)

AF:

0.0294

AC:

32650

AN:

1111984

Other (OTH)

AF:

0.0321

AC:

1940

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

2678

5356

8035

10713

13391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1274

2548

3822

5096

6370

<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:

0.0295

AC:

4486

AN:

152310

Hom.:

Cov.:

AF XY:

0.0294

AC XY:

2189

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0295

AC:

1224

AN:

41562

American (AMR)

AF:

0.0286

AC:

438

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0476

AC:

165

AN:

3470

East Asian (EAS)

AF:

0.0358

AC:

186

AN:

5192

South Asian (SAS)

AF:

0.0527

AC:

254

AN:

4822

European-Finnish (FIN)

AF:

0.0153

AC:

162

AN:

10616

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0292

AC:

1984

AN:

68028

Other (OTH)

AF:

0.0299

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

223

446

668

891

1114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0306

Hom.:

330

Bravo

AF:

0.0301

TwinsUK

AF:

0.0283

AC:

105

ALSPAC

AF:

0.0285

AC:

110

ESP6500AA

AF:

0.0327

AC:

144

ESP6500EA

AF:

0.0315

AC:

271

ExAC

AF:

0.0334

AC:

4055

Asia WGS

AF:

0.0370

AC:

128

AN:

3478

EpiCase

AF:

0.0302

EpiControl

AF:

0.0308

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia 33 (2)

not provided (1)

not specified (1)

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.046

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.0040

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.5

PhyloP100

-1.1

PrimateAI

Benign

0.32

PROVEAN

Benign

0.060

REVEL

Benign

0.018

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.064

ClinPred

0.0029

GERP RS

-7.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.018

gMVP

0.085

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over