chr3-45968515-T-C

Position:

chr3-45968515-T-C

Variant summary

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

The NM_024513.4(FYCO1):c.819A>G(p.Gln273=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,932 control chromosomes in the GnomAD database, including 14,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 1030 hom., cov: 33)

Exomes 𝑓: 0.12 ( 13016 hom. )

Consequence

FYCO1
NM_024513.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.535

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=-0.85).

BP6

Variant 3-45968515-T-C is Benign according to our data. Variant chr3-45968515-T-C is described in ClinVar as [Benign]. Clinvar id is 261737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-45968515-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.535 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/exons	MANE	UniProt
FYCO1	NM_024513.4 linkuse as main transcript	c.819A>G	p.Gln273=	synonymous_variant	8/18	ENST00000296137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYCO1	ENST00000296137.7 linkuse as main transcript	c.819A>G	p.Gln273=	synonymous_variant	8/18	1	NM_024513.4	P1	Q9BQS8-1

Frequencies

GnomAD3 genomes

AF:

0.0936

AC:

14247

AN:

152148

Hom.:

1031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0305

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.0694

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.0986

GnomAD3 exomes

AF:

0.127

AC:

31921

AN:

251290

Hom.:

3139

AF XY:

0.142

AC XY:

19246

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.0647

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.00272

Gnomad SAS exome

AF:

0.340

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.128

GnomAD4 exome

AF:

0.117

AC:

170480

AN:

1461666

Hom.:

13016

Cov.:

AF XY:

0.125

AC XY:

90809

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0295

Gnomad4 AMR exome

AF:

0.0669

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.00207

Gnomad4 SAS exome

AF:

0.335

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.0935

AC:

14243

AN:

152266

Hom.:

1030

Cov.:

AF XY:

0.0991

AC XY:

7382

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0305

Gnomad4 AMR

AF:

0.0692

Gnomad4 ASJ

AF:

0.196

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.342

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.111

Gnomad4 OTH

AF:

0.0994

Alfa

AF:

0.105

Hom.:

686

Bravo

AF:

0.0775

Asia WGS

AF:

0.172

AC:

599

AN:

3478

EpiCase

AF:

0.121

EpiControl

AF:

0.115

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 22, 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	May 10, 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

-0.85

CADD

Benign

2.9

DANN

Benign

0.23

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