rs144182297

Variant names:

• chr3-45958428-G-A
• NM_024513.4:c.3779C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-45958428-G-A
• chr3-45958428-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024513.4(FYCO1):​c.3779C>T​(p.Pro1260Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FYCO1 NM_024513.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08306807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYCO1	NM_024513.4	c.3779C>T	p.Pro1260Leu	missense_variant	Exon 13 of 18	ENST00000296137.7	NP_078789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYCO1	ENST00000296137.7	c.3779C>T	p.Pro1260Leu	missense_variant	Exon 13 of 18	1	NM_024513.4	ENSP00000296137.2
FYCO1	ENST00000433878.5	c.143C>T	p.Pro48Leu	missense_variant	Exon 1 of 7	2		ENSP00000388136.1
FYCO1	ENST00000438446.1	c.-209C>T		5_prime_UTR_variant	Exon 1 of 6	5		ENSP00000398517.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460226 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726414

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.2
DANN	Benign	0.61
DEOGEN2	Benign	0.0072	.;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.076
Sift	Benign	0.14	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0	.;B
Vest4		0.093
MutPred		0.21		Loss of phosphorylation at T1263 (P = 0.0774);Loss of phosphorylation at T1263 (P = 0.0774);
MVP		0.32
MPC		0.16
ClinPred		0.053	T
GERP RS		-3.3
Varity_R		0.024
gMVP		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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-45999920;