3-45952114-T-C

Position:

• chr3-45952114-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FYCO1	NM_024513.4	c.3944+3135A>G		intron_variant		ENST00000296137.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FYCO1	ENST00000296137.7	c.3944+3135A>G		intron_variant		1	NM_024513.4	P1
FYCO1	ENST00000433878.5	c.310+3135A>G		intron_variant		2
FYCO1	ENST00000438446.1	c.-44+3135A>G		intron_variant		5

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

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.490

Alfa AF: 0.508 Hom.: 18765

Bravo AF: 0.457

Asia WGS AF: 0.695 AC: 2417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.42

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: rs4682799; hg19: chr3-45993606;