rs34801630

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.2980G>A(p.Glu994Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0188 in 1,614,204 control chromosomes in the GnomAD database, including 1,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 481 hom., cov: 33)

Exomes 𝑓: 0.015 ( 559 hom. )

Consequence

FYCO1
NM_024513.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.82

Publications

13 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=0.001597017).

BP6

Variant 3-45966354-C-T is Benign according to our data. Variant chr3-45966354-C-T is described in ClinVar as Benign. ClinVar VariationId is 261726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024513.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FYCO1	NM_024513.4	MANE Select	c.2980G>A	p.Glu994Lys	missense	Exon 8 of 18	NP_078789.2
FYCO1	NM_001386421.1		c.2980G>A	p.Glu994Lys	missense	Exon 9 of 19	NP_001373350.1
FYCO1	NM_001386422.1		c.2980G>A	p.Glu994Lys	missense	Exon 8 of 18	NP_001373351.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYCO1	ENST00000296137.7	TSL:1 MANE Select	c.2980G>A	p.Glu994Lys	missense	Exon 8 of 18	ENSP00000296137.2

Frequencies

GnomAD3 genomes

AF:

0.0505

AC:

7684

AN:

152234

Hom.:

478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0315

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.0415

GnomAD2 exomes

AF:

0.0223

AC:

5581

AN:

250090

AF XY:

0.0185

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.0342

Gnomad ASJ exome

AF:

0.00745

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.0163

GnomAD4 exome

AF:

0.0155

AC:

22642

AN:

1461852

Hom.:

559

Cov.:

AF XY:

0.0145

AC XY:

10538

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.159

AC:

5332

AN:

33480

American (AMR)

AF:

0.0322

AC:

1439

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00831

AC:

217

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00373

AC:

322

AN:

86258

European-Finnish (FIN)

AF:

0.0112

AC:

600

AN:

53404

Middle Eastern (MID)

AF:

0.0125

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0122

AC:

13513

AN:

1111998

Other (OTH)

AF:

0.0190

AC:

1146

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1371

2743

4114

5486

6857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

608

1216

1824

2432

3040

<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:

0.0505

AC:

7701

AN:

152352

Hom.:

481

Cov.:

AF XY:

0.0480

AC XY:

3576

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.148

AC:

6134

AN:

41566

American (AMR)

AF:

0.0314

AC:

481

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00248

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00885

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0127

AC:

861

AN:

68038

Other (OTH)

AF:

0.0411

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

365

729

1094

1458

1823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0229

Hom.:

473

Bravo

AF:

0.0581

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.146

AC:

643

ESP6500EA

AF:

0.0123

AC:

106

ExAC

AF:

0.0245

AC:

2979

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0116

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 18 (2)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.025

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

PhyloP100

5.8

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.37

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.23

MPC

0.61

ClinPred

0.029

GERP RS

5.5

Varity_R

0.29

gMVP

0.27

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over