3-45990465-C-T

Variant names:

• chr3-45990465-C-T
• rs2133660
• NM_024513.4:c.-113+5257G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024513.4(FYCO1):​c.-113+5257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,014 control chromosomes in the GnomAD database, including 26,122 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 0.56 (26122 hom., cov: 32)
• Consequence: FYCO1 NM_024513.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYCO1	NM_024513.4	c.-113+5257G>A		intron_variant	Intron 1 of 17	ENST00000296137.7	NP_078789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYCO1	ENST00000296137.7	c.-113+5257G>A		intron_variant	Intron 1 of 17	1	NM_024513.4	ENSP00000296137.2
FYCO1	ENST00000471739.1	n.103+5257G>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84770 AN: 151896 Hom.: 26109 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.558 AC: 84819 AN: 152014 Hom.: 26122 Cov.: 32 AF XY: 0.562 AC XY: 41758 AN XY: 74302

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.652

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.605

Alfa AF: 0.607 Hom.: 13808

Bravo AF: 0.557

Asia WGS AF: 0.711 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.39

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: rs2133660; hg19: chr3-46031957;