3-45918587-C-A

Position:

• chr3-45918587-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024513.4(FYCO1):​c.*3178G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,108 control chromosomes in the GnomAD database, including 53,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (53774 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: FYCO1 NM_024513.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.134

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-45918587-C-A is Benign according to our data. Variant chr3-45918587-C-A is described in ClinVar as [Benign]. Clinvar id is 345445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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	UniProt
FYCO1	NM_024513.4	c.*3178G>T		3_prime_UTR_variant	18/18	ENST00000296137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYCO1	ENST00000296137.7	c.*3178G>T		3_prime_UTR_variant	18/18	1	NM_024513.4	P1
FYCO1	ENST00000433878.5	c.*2831G>T		3_prime_UTR_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127064 AN: 151988 Hom.: 53712 Cov.: 31

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.848

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.836 AC: 127186 AN: 152106 Hom.: 53774 Cov.: 31 AF XY: 0.840 AC XY: 62431 AN XY: 74354

Gnomad4 AFR AF: 0.933

Gnomad4 AMR AF: 0.888

Gnomad4 ASJ AF: 0.846

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.850

Alfa AF: 0.787 Hom.: 43775

Bravo AF: 0.849

Asia WGS AF: 0.965 AC: 3355 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cataract 18 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.37

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

Other links and lift over

dbSNP: rs1047444; hg19: chr3-45960079;