10-97744873-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 130787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-97744873-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFYVE27	NM_001385875.1 link	c.413G>T	p.Gly138Val	missense_variant	Exon 4 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.413G>T	p.Gly138Val	missense_variant	Exon 4 of 13		NM_001385875.1	ENSP00000506975.1		Q5T4F4-1

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

GnomAD3 exomes

AF:

0.708

AC:

170583

AN:

240950

Hom.:

61363

AF XY:

0.713

AC XY:

92875

AN XY:

130306

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 SAS exome

AF:

0.694

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

Gnomad4 AFR exome

AF:

0.759

Gnomad4 AMR exome

AF:

0.568

Gnomad4 ASJ exome

AF:

0.802

Gnomad4 EAS exome

AF:

0.561

Gnomad4 SAS exome

AF:

0.694

Gnomad4 FIN exome

AF:

0.796

Gnomad4 NFE exome

AF:

0.754

Gnomad4 OTH exome

AF:

0.732

GnomAD4 genome

AF:

0.741

AC:

112767

AN:

152142

Hom.:

42040

Cov.:

AF XY:

0.740

AC XY:

55064

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.760

Gnomad4 AMR

AF:

0.645

Gnomad4 ASJ

AF:

0.801

Gnomad4 EAS

AF:

0.526

Gnomad4 SAS

AF:

0.710

Gnomad4 FIN

AF:

0.801

Gnomad4 NFE

AF:

0.758

Gnomad4 OTH

AF:

0.733

Alfa

AF:

0.750

Hom.:

99009

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

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 02, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.11

DEOGEN2

Benign

0.0059

.;.;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.31

T;T;T;T;T

MetaRNN

Benign

9.5e-7

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.0

.;.;N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

1.7

N;N;N;.;N

REVEL

Benign

0.096

Sift

Benign

1.0

T;T;T;.;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

.;.;B;B;B

Vest4

0.26

ClinPred

0.0035

GERP RS

4.5

Varity_R

0.14

gMVP

0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over