NM_024513.4:c.1335G>A

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.1335G>A(p.Leu445Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,614,032 control chromosomes in the GnomAD database, including 30,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2226 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27909 hom. )

Consequence

FYCO1
NM_024513.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.103

Publications

22 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=-0.62).

BP6

Variant 3-45967999-C-T is Benign according to our data. Variant chr3-45967999-C-T is described in ClinVar as [Benign]. Clinvar id is 261719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.103 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYCO1	NM_024513.4 link	c.1335G>A	p.Leu445Leu	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.1335G>A	p.Leu445Leu	synonymous_variant	Exon 8 of 18	1	NM_024513.4	ENSP00000296137.2		Q9BQS8-1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

23996

AN:

152042

Hom.:

2223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0641

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.192

GnomAD2 exomes

AF:

0.183

AC:

46021

AN:

251450

AF XY:

0.186

show subpopulations

Gnomad AFR exome

AF:

0.0604

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.285

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.191

AC:

279749

AN:

1461872

Hom.:

27909

Cov.:

AF XY:

0.191

AC XY:

139213

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0586

AC:

1963

AN:

33480

American (AMR)

AF:

0.146

AC:

6545

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

5426

AN:

26136

East Asian (EAS)

AF:

0.298

AC:

11832

AN:

39700

South Asian (SAS)

AF:

0.155

AC:

13361

AN:

86258

European-Finnish (FIN)

AF:

0.180

AC:

9598

AN:

53408

Middle Eastern (MID)

AF:

0.239

AC:

1379

AN:

5768

European-Non Finnish (NFE)

AF:

0.196

AC:

218066

AN:

1112002

Other (OTH)

AF:

0.192

AC:

11579

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

15725

31450

47174

62899

78624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.158

AC:

23997

AN:

152160

Hom.:

2226

Cov.:

AF XY:

0.157

AC XY:

11674

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0641

AC:

2661

AN:

41542

American (AMR)

AF:

0.170

AC:

2601

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

707

AN:

3470

East Asian (EAS)

AF:

0.279

AC:

1441

AN:

5156

South Asian (SAS)

AF:

0.154

AC:

741

AN:

4822

European-Finnish (FIN)

AF:

0.168

AC:

1778

AN:

10592

Middle Eastern (MID)

AF:

0.260

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.199

AC:

13548

AN:

67960

Other (OTH)

AF:

0.190

AC:

402

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

993

1985

2978

3970

4963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.178

Hom.:

1277

Bravo

AF:

0.159

Asia WGS

AF:

0.189

AC:

655

AN:

3478

EpiCase

AF:

0.208

EpiControl

AF:

0.202

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 18

Benign:2

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 24, 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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.62

CADD

Benign

0.58

(source)

DANN

Benign

0.49

PhyloP100

0.10

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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NM_024513.4:c.1335G>A

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