3-45952114-T-C

Variant names:

• chr3-45952114-T-C
• rs4682799
• NM_024513.4:c.3944+3135A>G

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+3135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,906 control chromosomes in the GnomAD database, including 18,407 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 0.47 (18407 hom., cov: 31)
• Consequence: FYCO1 NM_024513.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• Publications: 11 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.693 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+3135A>G		intron	N/A	NP_078789.2	Q9BQS8-1
	FYCO1	NM_001386421.1		c.3944+3135A>G		intron	N/A	NP_001373350.1	Q9BQS8-1
	FYCO1	NM_001386422.1		c.3944+3135A>G		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+3135A>G		intron	N/A	ENSP00000296137.2	Q9BQS8-1
	FYCO1	ENST00000874259.1		c.3944+3135A>G		intron	N/A	ENSP00000544318.1
	FYCO1	ENST00000965269.1		c.3944+3135A>G		intron	N/A	ENSP00000635328.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71763 AN: 151788 Hom.: 18390 Cov.: 31

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.473 AC: 71807 AN: 151906 Hom.: 18407 Cov.: 31 AF XY: 0.484 AC XY: 35971 AN XY: 74272

African (AFR) AF: 0.287 AC: 11867 AN: 41394

American (AMR) AF: 0.591 AC: 9017 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2022 AN: 3468

East Asian (EAS) AF: 0.664 AC: 3435 AN: 5176

South Asian (SAS) AF: 0.713 AC: 3427 AN: 4808

European-Finnish (FIN) AF: 0.582 AC: 6135 AN: 10542

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.503 AC: 34191 AN: 67944

Other (OTH) AF: 0.490 AC: 1034 AN: 2112

Alfa AF: 0.499 Hom.: 24099

Bravo AF: 0.457

Asia WGS AF: 0.695 AC: 2417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		-0.36
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: rs4682799; hg19: chr3-45993606;