rs13059238

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_024513.4(FYCO1):c.3001A>G(p.Asn1001Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,892 control chromosomes in the GnomAD database, including 14,017 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1001E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.093 ( 1007 hom., cov: 33)

Exomes 𝑓: 0.12 ( 13010 hom. )

Consequence

FYCO1
NM_024513.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.912

Publications

29 publications found

Variant links:

Genes affected

FYCO1 (HGNC:14673): (FYVE and coiled-coil domain autophagy adaptor 1) The gene encodes a Rab7 adapter protein that is implicated in the microtubule transport of autophagosomes. The encoded protein contains a RUN domain, a FYVE-type zinc finger domain, and Golgi dynamics (GOLD) domain. The encoded protein plays a role in microtubule plus end-directed transport of autophagic vesicles through interactions with the small GTPase Rab7, phosphatidylinositol-3-phosphate (PI3P), the autophagosome marker LC3, and the kinesin KIF5. Mutations in this gene are associated with inclusion body myositis (IBM) and autosomal recessive congenital cataracts (CATC2). [provided by RefSeq, Aug 2020]

FYCO1 Gene-Disease associations (from GenCC):

cataract 18
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
total early-onset cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FYCO1 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=0.0027463734).

BP6

Variant 3-45966333-T-C is Benign according to our data. Variant chr3-45966333-T-C is described in ClinVar as Benign. ClinVar VariationId is 261728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYCO1	NM_024513.4 link	c.3001A>G	p.Asn1001Asp	missense_variant	Exon 8 of 18	ENST00000296137.7	NP_078789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYCO1	ENST00000296137.7 link	c.3001A>G	p.Asn1001Asp	missense_variant	Exon 8 of 18	1	NM_024513.4	ENSP00000296137.2

Frequencies

GnomAD3 genomes

AF:

0.0934

AC:

14209

AN:

152086

Hom.:

1008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0306

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.0693

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.00367

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.0981

GnomAD2 exomes

AF:

0.127

AC:

31697

AN:

249768

AF XY:

0.142

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.0647

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.00266

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.128

GnomAD4 exome

AF:

0.117

AC:

170442

AN:

1461688

Hom.:

13010

Cov.:

AF XY:

0.125

AC XY:

90798

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.0294

AC:

985

AN:

33478

American (AMR)

AF:

0.0669

AC:

2990

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

5093

AN:

26126

East Asian (EAS)

AF:

0.00204

AC:

AN:

39698

South Asian (SAS)

AF:

0.335

AC:

28891

AN:

86248

European-Finnish (FIN)

AF:

0.144

AC:

7685

AN:

53386

Middle Eastern (MID)

AF:

0.198

AC:

1140

AN:

5764

European-Non Finnish (NFE)

AF:

0.105

AC:

116269

AN:

1111878

Other (OTH)

AF:

0.121

AC:

7308

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

8226

16452

24677

32903

41129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4178

8356

12534

16712

20890

<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:

0.0933

AC:

14205

AN:

152204

Hom.:

1007

Cov.:

AF XY:

0.0989

AC XY:

7360

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0305

AC:

1268

AN:

41548

American (AMR)

AF:

0.0691

AC:

1058

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

678

AN:

3468

East Asian (EAS)

AF:

0.00368

AC:

AN:

5166

South Asian (SAS)

AF:

0.342

AC:

1650

AN:

4828

European-Finnish (FIN)

AF:

0.144

AC:

1533

AN:

10610

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7529

AN:

67964

Other (OTH)

AF:

0.0990

AC:

209

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

679

1359

2038

2718

3397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.0877

Hom.:

451

Bravo

AF:

0.0775

TwinsUK

AF:

0.100

AC:

371

ALSPAC

AF:

0.0996

AC:

384

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.00407

AC:

ExAC

AF:

0.129

AC:

15646

Asia WGS

AF:

0.172

AC:

599

AN:

3478

EpiCase

AF:

0.121

EpiControl

AF:

0.115

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 18

Benign:3

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. -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

0.062

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.0012

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.13

T;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.1

N;N

PhyloP100

0.91

PrimateAI

Benign

0.32

PROVEAN

Benign

0.49

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.012

MPC

0.18

ClinPred

0.00036

GERP RS

2.3

Varity_R

0.046

gMVP

0.060

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