rs1545985

Variant names:

• chr3-45963986-G-A
• rs1545985
• NM_024513.4:c.3269+350C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024513.4(FYCO1):​c.3269+350C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 152,164 control chromosomes in the GnomAD database, including 39,028 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (39028 hom., cov: 33)
• Consequence: FYCO1 NM_024513.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 20 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYCO1	NM_024513.4	c.3269+350C>T		intron_variant	Intron 10 of 17	ENST00000296137.7	NP_078789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYCO1	ENST00000296137.7	c.3269+350C>T		intron_variant	Intron 10 of 17	1	NM_024513.4	ENSP00000296137.2

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107493 AN: 152046 Hom.: 38980 Cov.: 33

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.717

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.707 AC: 107605 AN: 152164 Hom.: 39028 Cov.: 33 AF XY: 0.708 AC XY: 52634 AN XY: 74380

African (AFR) AF: 0.819 AC: 34018 AN: 41536

American (AMR) AF: 0.797 AC: 12187 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2207 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5171 AN: 5194

South Asian (SAS) AF: 0.586 AC: 2819 AN: 4812

European-Finnish (FIN) AF: 0.621 AC: 6557 AN: 10554

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42543 AN: 67980

Other (OTH) AF: 0.719 AC: 1522 AN: 2116

Alfa AF: 0.653 Hom.: 51229

Bravo AF: 0.730

Asia WGS AF: 0.791 AC: 2749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.78
DANN	Benign	0.78
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1545985; hg19: chr3-46005478;