3-45952481-C-T

Position:

• chr3-45952481-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FYCO1	NM_024513.4	c.3944+2768G>A		intron_variant		ENST00000296137.7	NP_078789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FYCO1	ENST00000296137.7	c.3944+2768G>A		intron_variant		1	NM_024513.4	ENSP00000296137.2
FYCO1	ENST00000433878.5	c.308+2768G>A		intron_variant		2		ENSP00000388136.1
FYCO1	ENST00000438446.1	c.-44+2768G>A		intron_variant		5		ENSP00000398517.1

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

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.388

Alfa AF: 0.311 Hom.: 1255

Bravo AF: 0.379

Asia WGS AF: 0.518 AC: 1800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.45

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: rs1552489; hg19: chr3-45993973;