rs4682801

Positions:

chr3-45979726-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024513.4(FYCO1):c.267C>A(p.Arg89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 1,613,298 control chromosomes in the GnomAD database, including 484,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 39463 hom., cov: 33)

Exomes 𝑓: 0.78 ( 445142 hom. )

Consequence

FYCO1
NM_024513.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.344

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 3-45979726-G-T is Benign according to our data. Variant chr3-45979726-G-T is described in ClinVar as [Benign]. Clinvar id is 261723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-45979726-G-T is described in Lovd as [Benign]. Variant chr3-45979726-G-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.344 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FYCO1	NM_024513.4 linkuse as main transcript	c.267C>A	p.Arg89=	synonymous_variant	4/18	ENST00000296137.7	NP_078789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FYCO1	ENST00000296137.7 linkuse as main transcript	c.267C>A	p.Arg89=	synonymous_variant	4/18	1	NM_024513.4	ENSP00000296137	P1	Q9BQS8-1

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

106144

AN:

152014

Hom.:

39435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.429

Gnomad AMI

AF:

0.658

Gnomad AMR

AF:

0.841

Gnomad ASJ

AF:

0.840

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.909

Gnomad FIN

AF:

0.809

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.766

Gnomad OTH

AF:

0.751

GnomAD3 exomes

AF:

0.808

AC:

203219

AN:

251496

Hom.:

84115

AF XY:

0.815

AC XY:

110782

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.425

Gnomad AMR exome

AF:

0.902

Gnomad ASJ exome

AF:

0.846

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.900

Gnomad FIN exome

AF:

0.810

Gnomad NFE exome

AF:

0.774

Gnomad OTH exome

AF:

0.814

GnomAD4 exome

AF:

0.776

AC:

1134220

AN:

1461166

Hom.:

445142

Cov.:

AF XY:

0.781

AC XY:

568002

AN XY:

726918

show subpopulations

Gnomad4 AFR exome

AF:

0.423

Gnomad4 AMR exome

AF:

0.892

Gnomad4 ASJ exome

AF:

0.845

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.899

Gnomad4 FIN exome

AF:

0.806

Gnomad4 NFE exome

AF:

0.760

Gnomad4 OTH exome

AF:

0.790

GnomAD4 genome

AF:

0.698

AC:

106218

AN:

152132

Hom.:

39463

Cov.:

AF XY:

0.708

AC XY:

52671

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.430

Gnomad4 AMR

AF:

0.841

Gnomad4 ASJ

AF:

0.840

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.909

Gnomad4 FIN

AF:

0.809

Gnomad4 NFE

AF:

0.766

Gnomad4 OTH

AF:

0.754

Alfa

AF:

0.758

Hom.:

56853

Bravo

AF:

0.687

Asia WGS

AF:

0.939

AC:

3262

AN:

3478

EpiCase

AF:

0.781

EpiControl

AF:

0.781

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 18

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 27, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.99

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over