3-45975359-A-T

Variant names:

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.289-14T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,599,240 control chromosomes in the GnomAD database, including 148,401 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11782 hom., cov: 32)

Exomes 𝑓: 0.43 ( 136619 hom. )

Consequence

FYCO1
NM_024513.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.51

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-45975359-A-T is Benign according to our data. Variant chr3-45975359-A-T is described in ClinVar as Benign. ClinVar VariationId is 261725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYCO1	NM_024513.4 link	c.289-14T>A		intron_variant	Intron 4 of 17	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.289-14T>A		intron_variant	Intron 4 of 17	1	NM_024513.4	ENSP00000296137.2		Q9BQS8-1

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54302

AN:

151978

Hom.:

11769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.517

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.675

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.368

GnomAD2 exomes

AF:

0.442

AC:

110744

AN:

250712

AF XY:

0.435

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.605

Gnomad ASJ exome

AF:

0.390

Gnomad EAS exome

AF:

0.669

Gnomad FIN exome

AF:

0.475

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.428

GnomAD4 exome

AF:

0.428

AC:

619019

AN:

1447144

Hom.:

136619

Cov.:

AF XY:

0.425

AC XY:

306180

AN XY:

720976

show subpopulations

African (AFR)

AF:

0.104

AC:

3457

AN:

33112

American (AMR)

AF:

0.593

AC:

26494

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

10158

AN:

26054

East Asian (EAS)

AF:

0.642

AC:

25443

AN:

39632

South Asian (SAS)

AF:

0.360

AC:

30902

AN:

85950

European-Finnish (FIN)

AF:

0.463

AC:

24672

AN:

53288

Middle Eastern (MID)

AF:

0.346

AC:

1990

AN:

5752

European-Non Finnish (NFE)

AF:

0.428

AC:

470339

AN:

1098820

Other (OTH)

AF:

0.427

AC:

25564

AN:

59892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

16650

33300

49950

66600

83250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14334

28668

43002

57336

71670

<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:

0.357

AC:

54329

AN:

152096

Hom.:

11782

Cov.:

AF XY:

0.364

AC XY:

27086

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.119

AC:

4956

AN:

41512

American (AMR)

AF:

0.517

AC:

7905

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1349

AN:

3466

East Asian (EAS)

AF:

0.675

AC:

3481

AN:

5160

South Asian (SAS)

AF:

0.367

AC:

1772

AN:

4826

European-Finnish (FIN)

AF:

0.474

AC:

5007

AN:

10556

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.422

AC:

28647

AN:

67964

Other (OTH)

AF:

0.374

AC:

792

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1612

3225

4837

6450

8062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.384

Hom.:

2241

Bravo

AF:

0.350

Asia WGS

AF:

0.512

AC:

1781

AN:

3478

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. -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 31, 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

- -

Jul 21, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.80

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

1.5

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