dbSNP rs367690473: FYCO1:p.Gly1235Gly (chr3-45958502-G-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_StrongBP7BS1BS2

The NM_024513.4(FYCO1):c.3705C>A(p.Gly1235Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000664 in 1,614,168 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00045 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00069 ( 14 hom. )

Consequence

FYCO1
NM_024513.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0510

Publications

0 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 -17 ACMG points.

BP6

Variant 3-45958502-G-T is Benign according to our data. Variant chr3-45958502-G-T is described in ClinVar as Benign. ClinVar VariationId is 261733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.051 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000453 (69/152338) while in subpopulation SAS AF = 0.0139 (67/4828). AF 95% confidence interval is 0.0112. There are 2 homozygotes in GnomAd4. There are 50 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

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	UniProt
FYCO1	NM_024513.4	MANE Select	c.3705C>A	p.Gly1235Gly	synonymous	Exon 13 of 18	NP_078789.2	Q9BQS8-1
FYCO1	NM_001386421.1		c.3705C>A	p.Gly1235Gly	synonymous	Exon 14 of 19	NP_001373350.1	Q9BQS8-1
FYCO1	NM_001386422.1		c.3705C>A	p.Gly1235Gly	synonymous	Exon 13 of 18	NP_001373351.1	Q9BQS8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FYCO1	ENST00000296137.7	TSL:1 MANE Select	c.3705C>A	p.Gly1235Gly	synonymous	Exon 13 of 18	ENSP00000296137.2	Q9BQS8-1
FYCO1	ENST00000874259.1		c.3705C>A	p.Gly1235Gly	synonymous	Exon 14 of 19	ENSP00000544318.1
FYCO1	ENST00000965269.1		c.3705C>A	p.Gly1235Gly	synonymous	Exon 13 of 18	ENSP00000635328.1

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00141

AC:

355

AN:

251390

AF XY:

0.00190

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000686

AC:

1003

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000960

AC XY:

698

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0110

AC:

952

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112006

Other (OTH)

AF:

0.000778

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

155

233

310

388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000453

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.0139

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.000106

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 18 (2)

FYCO1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.1

(source)

DANN

Benign

0.53

PhyloP100

0.051

PromoterAI

-0.0037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=292/8

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over