NM_024513.4:c.2739C>T

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.2739C>T(p.Cys913Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,614,126 control chromosomes in the GnomAD database, including 13,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 993 hom., cov: 33)

Exomes 𝑓: 0.12 ( 12770 hom. )

Consequence

FYCO1
NM_024513.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.421

Publications

17 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=-0.87).

BP6

Variant 3-45966595-G-A is Benign according to our data. Variant chr3-45966595-G-A is described in ClinVar as Benign. ClinVar VariationId is 261724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.421 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.2739C>T	p.Cys913Cys	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.2739C>T	p.Cys913Cys	synonymous_variant	Exon 8 of 18	1	NM_024513.4	ENSP00000296137.2		Q9BQS8-1

Frequencies

GnomAD3 genomes

AF:

0.0892

AC:

13575

AN:

152198

Hom.:

994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.0646

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.0904

GnomAD2 exomes

AF:

0.125

AC:

31213

AN:

250258

AF XY:

0.140

show subpopulations

Gnomad AFR exome

AF:

0.0186

Gnomad AMR exome

AF:

0.0612

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.00272

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.115

AC:

168290

AN:

1461810

Hom.:

12770

Cov.:

AF XY:

0.123

AC XY:

89745

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.0179

AC:

598

AN:

33480

American (AMR)

AF:

0.0631

AC:

2822

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

4710

AN:

26136

East Asian (EAS)

AF:

0.00204

AC:

AN:

39700

South Asian (SAS)

AF:

0.334

AC:

28849

AN:

86256

European-Finnish (FIN)

AF:

0.144

AC:

7689

AN:

53344

Middle Eastern (MID)

AF:

0.189

AC:

1089

AN:

5768

European-Non Finnish (NFE)

AF:

0.104

AC:

115361

AN:

1112008

Other (OTH)

AF:

0.117

AC:

7091

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

10377

20754

31132

41509

51886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4140

8280

12420

16560

20700

<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:

0.0891

AC:

13570

AN:

152316

Hom.:

993

Cov.:

AF XY:

0.0950

AC XY:

7076

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0197

AC:

820

AN:

41590

American (AMR)

AF:

0.0645

AC:

986

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

629

AN:

3464

East Asian (EAS)

AF:

0.00366

AC:

AN:

5186

South Asian (SAS)

AF:

0.341

AC:

1647

AN:

4826

European-Finnish (FIN)

AF:

0.145

AC:

1542

AN:

10616

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.110

AC:

7474

AN:

68020

Other (OTH)

AF:

0.0914

AC:

193

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

628

1256

1884

2512

3140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.102

Hom.:

1544

Bravo

AF:

0.0723

Asia WGS

AF:

0.170

AC:

591

AN:

3478

EpiCase

AF:

0.119

EpiControl

AF:

0.113

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 18

Benign:3

Jan 12, 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

-0.87

CADD

Benign

0.68

(source)

DANN

Benign

0.31

PhyloP100

-0.42

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)

0.010

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