rs10882993

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_001385875.1(ZFYVE27):c.413G>T(p.Gly138Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 1,607,502 control chromosomes in the GnomAD database, including 444,151 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42040 hom., cov: 34)

Exomes 𝑓: 0.74 ( 402111 hom. )

Consequence

ZFYVE27
NM_001385875.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.38

Publications

40 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=9.5281155E-7).

BP6

Variant 10-97744873-G-T is Benign according to our data. Variant chr10-97744873-G-T is described in ClinVar as Benign. ClinVar VariationId is 130787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 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.413G>T	p.Gly138Val	missense	Exon 4 of 13	NP_001372804.1	Q5T4F4-1
ZFYVE27	NM_001385876.1		c.452G>T	p.Gly151Val	missense	Exon 5 of 13	NP_001372805.1
ZFYVE27	NM_001002261.4		c.413G>T	p.Gly138Val	missense	Exon 4 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.413G>T	p.Gly138Val	missense	Exon 4 of 13	ENSP00000506975.1	Q5T4F4-1
ZFYVE27	ENST00000393677.8	TSL:1	c.413G>T	p.Gly138Val	missense	Exon 4 of 13	ENSP00000377282.3	Q5T4F4-1
ZFYVE27	ENST00000423811.3	TSL:5	c.413G>T	p.Gly138Val	missense	Exon 4 of 13	ENSP00000409594.2	Q5T4F4-3

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112678

AN:

152026

Hom.:

41999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.760

Gnomad AMI

AF:

0.700

Gnomad AMR

AF:

0.647

Gnomad ASJ

AF:

0.801

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.709

Gnomad FIN

AF:

0.801

Gnomad MID

AF:

0.815

Gnomad NFE

AF:

0.758

Gnomad OTH

AF:

0.731

GnomAD2 exomes

AF:

0.708

AC:

170583

AN:

240950

AF XY:

0.713

show subpopulations

Gnomad AFR exome

AF:

0.755

Gnomad AMR exome

AF:

0.559

Gnomad ASJ exome

AF:

0.797

Gnomad EAS exome

AF:

0.504

Gnomad FIN exome

AF:

0.797

Gnomad NFE exome

AF:

0.759

Gnomad OTH exome

AF:

0.733

GnomAD4 exome

AF:

0.741

AC:

1078544

AN:

1455360

Hom.:

402111

Cov.:

AF XY:

0.741

AC XY:

536147

AN XY:

723486

show subpopulations

African (AFR)

AF:

0.759

AC:

25356

AN:

33424

American (AMR)

AF:

0.568

AC:

24994

AN:

43990

Ashkenazi Jewish (ASJ)

AF:

0.802

AC:

20838

AN:

25988

East Asian (EAS)

AF:

0.561

AC:

22232

AN:

39606

South Asian (SAS)

AF:

0.694

AC:

59225

AN:

85378

European-Finnish (FIN)

AF:

0.796

AC:

41751

AN:

52456

Middle Eastern (MID)

AF:

0.765

AC:

4317

AN:

5640

European-Non Finnish (NFE)

AF:

0.754

AC:

835862

AN:

1108794

Other (OTH)

AF:

0.732

AC:

43969

AN:

60084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

17637

35275

52912

70550

88187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20190

40380

60570

80760

100950

<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:

0.741

AC:

112767

AN:

152142

Hom.:

42040

Cov.:

AF XY:

0.740

AC XY:

55064

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.760

AC:

31569

AN:

41520

American (AMR)

AF:

0.645

AC:

9867

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.801

AC:

2779

AN:

3470

East Asian (EAS)

AF:

0.526

AC:

2704

AN:

5142

South Asian (SAS)

AF:

0.710

AC:

3429

AN:

4830

European-Finnish (FIN)

AF:

0.801

AC:

8486

AN:

10594

Middle Eastern (MID)

AF:

0.818

AC:

239

AN:

292

European-Non Finnish (NFE)

AF:

0.758

AC:

51510

AN:

67988

Other (OTH)

AF:

0.733

AC:

1548

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1506

3012

4519

6025

7531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.747

Hom.:

196914

Bravo

AF:

0.728

TwinsUK

AF:

0.752

AC:

2787

ALSPAC

AF:

0.748

AC:

2883

ESP6500AA

AF:

0.767

AC:

3380

ESP6500EA

AF:

0.762

AC:

6553

ExAC

AF:

0.710

AC:

86162

Asia WGS

AF:

0.657

AC:

2286

AN:

3478

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 (2)

not specified (2)

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.0059

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.31

MetaRNN

Benign

9.5e-7

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.0

PhyloP100

2.4

PrimateAI

Uncertain

0.61

PROVEAN

Benign

1.7

REVEL

Benign

0.096

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.26

ClinPred

0.0035

GERP RS

4.5

Varity_R

0.14

gMVP

0.31

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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