rs34147726

Variant summary

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

The NM_024513.4(FYCO1):​c.1206G>A​(p.Glu402Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,614,100 control chromosomes in the GnomAD database, including 3,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 2053 hom., cov: 32)
Exomes 𝑓: 0.0085 ( 1788 hom. )

Consequence

FYCO1
NM_024513.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.150
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]

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=-0.62).
BP6
Variant 3-45968128-C-T is Benign according to our data. Variant chr3-45968128-C-T is described in ClinVar as [Benign]. Clinvar id is 261718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.15 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FYCO1NM_024513.4 linkuse as main transcriptc.1206G>A p.Glu402Glu synonymous_variant 8/18 ENST00000296137.7 NP_078789.2 Q9BQS8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FYCO1ENST00000296137.7 linkuse as main transcriptc.1206G>A p.Glu402Glu synonymous_variant 8/181 NM_024513.4 ENSP00000296137.2 Q9BQS8-1

Frequencies

GnomAD3 genomes
AF:
0.0883
AC:
13428
AN:
152130
Hom.:
2052
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.310
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0292
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000662
Gnomad OTH
AF:
0.0583
GnomAD3 exomes
AF:
0.0223
AC:
5610
AN:
251380
Hom.:
809
AF XY:
0.0161
AC XY:
2186
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.314
Gnomad AMR exome
AF:
0.0114
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000405
Gnomad OTH exome
AF:
0.00993
GnomAD4 exome
AF:
0.00855
AC:
12493
AN:
1461852
Hom.:
1788
Cov.:
79
AF XY:
0.00728
AC XY:
5296
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.314
Gnomad4 AMR exome
AF:
0.0140
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000406
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000174
Gnomad4 OTH exome
AF:
0.0181
GnomAD4 genome
AF:
0.0883
AC:
13446
AN:
152248
Hom.:
2053
Cov.:
32
AF XY:
0.0847
AC XY:
6304
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.309
Gnomad4 AMR
AF:
0.0292
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000662
Gnomad4 OTH
AF:
0.0577
Alfa
AF:
0.0400
Hom.:
448
Bravo
AF:
0.102
Asia WGS
AF:
0.0140
AC:
51
AN:
3478
EpiCase
AF:
0.000600
EpiControl
AF:
0.000652

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Cataract 18 Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 20, 2024- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 31, 2018This 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. -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
CADD
Benign
1.5
DANN
Benign
0.27

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.

Other links and lift over

dbSNP: rs34147726; hg19: chr3-46009620; API