rs13071283

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024513.4(FYCO1):c.819A>G(p.Gln273Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,932 control chromosomes in the GnomAD database, including 14,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 1030 hom., cov: 33)

Exomes 𝑓: 0.12 ( 13016 hom. )

Consequence

FYCO1
NM_024513.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.535

Publications

15 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-45968515-T-C is Benign according to our data. Variant chr3-45968515-T-C is described in ClinVar as [Benign]. Clinvar id is 261737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.535 with no splicing effect.

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.819A>G	p.Gln273Gln	synonymous_variant	Exon 8 of 18	ENST00000296137.7	NP_078789.2	Q9BQS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYCO1	ENST00000296137.7 link	c.819A>G	p.Gln273Gln	synonymous_variant	Exon 8 of 18	1	NM_024513.4	ENSP00000296137.2		Q9BQS8-1

Frequencies

GnomAD3 genomes

AF:

0.0936

AC:

14247

AN:

152148

Hom.:

1031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0305

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.0694

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.0986

GnomAD2 exomes

AF:

0.127

AC:

31921

AN:

251290

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:

0.00272

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.128

GnomAD4 exome

AF:

0.117

AC:

170480

AN:

1461666

Hom.:

13016

Cov.:

AF XY:

0.125

AC XY:

90809

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.0295

AC:

986

AN:

33480

American (AMR)

AF:

0.0669

AC:

2991

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

5096

AN:

26136

East Asian (EAS)

AF:

0.00207

AC:

AN:

39700

South Asian (SAS)

AF:

0.335

AC:

28894

AN:

86258

European-Finnish (FIN)

AF:

0.144

AC:

7651

AN:

53216

Middle Eastern (MID)

AF:

0.198

AC:

1142

AN:

5768

European-Non Finnish (NFE)

AF:

0.105

AC:

116326

AN:

1111994

Other (OTH)

AF:

0.121

AC:

7312

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

10267

20534

30801

41068

51335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0935

AC:

14243

AN:

152266

Hom.:

1030

Cov.:

AF XY:

0.0991

AC XY:

7382

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0305

AC:

1267

AN:

41570

American (AMR)

AF:

0.0692

AC:

1059

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

681

AN:

3468

East Asian (EAS)

AF:

0.00367

AC:

AN:

5180

South Asian (SAS)

AF:

0.342

AC:

1648

AN:

4816

European-Finnish (FIN)

AF:

0.145

AC:

1539

AN:

10608

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7558

AN:

68010

Other (OTH)

AF:

0.0994

AC:

210

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

665

1330

1994

2659

3324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.105

Hom.:

758

Bravo

AF:

0.0775

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. -

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

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

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.9

(source)

DANN

Benign

0.23

PhyloP100

-0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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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rs13071283

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