3-45952481-C-T

Variant names:

• chr3-45952481-C-T
• rs1552489
• NM_024513.4:c.3944+2768G>A

Variant summary

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

The NM_024513.4(FYCO1):​c.3944+2768G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,968 control chromosomes in the GnomAD database, including 11,800 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 0.38 (11800 hom., cov: 31)
• Consequence: FYCO1 NM_024513.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024513.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYCO1	NM_024513.4	MANE Select	c.3944+2768G>A		intron	N/A	NP_078789.2	Q9BQS8-1
	FYCO1	NM_001386421.1		c.3944+2768G>A		intron	N/A	NP_001373350.1	Q9BQS8-1
	FYCO1	NM_001386422.1		c.3944+2768G>A		intron	N/A	NP_001373351.1	Q9BQS8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYCO1	ENST00000296137.7	TSL:1 MANE Select	c.3944+2768G>A		intron	N/A	ENSP00000296137.2	Q9BQS8-1
	FYCO1	ENST00000874259.1		c.3944+2768G>A		intron	N/A	ENSP00000544318.1
	FYCO1	ENST00000965269.1		c.3944+2768G>A		intron	N/A	ENSP00000635328.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57430 AN: 151850 Hom.: 11784 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.378 AC: 57481 AN: 151968 Hom.: 11800 Cov.: 31 AF XY: 0.384 AC XY: 28555 AN XY: 74282

African (AFR) AF: 0.255 AC: 10572 AN: 41442

American (AMR) AF: 0.519 AC: 7925 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1341 AN: 3466

East Asian (EAS) AF: 0.661 AC: 3416 AN: 5168

South Asian (SAS) AF: 0.361 AC: 1735 AN: 4800

European-Finnish (FIN) AF: 0.437 AC: 4611 AN: 10546

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26647 AN: 67966

Other (OTH) AF: 0.388 AC: 816 AN: 2102

Alfa AF: 0.308 Hom.: 1281

Bravo AF: 0.379

Asia WGS AF: 0.518 AC: 1800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.45
PhyloP100		-2.0
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: rs1552489; hg19: chr3-45993973;