chr3-45923752-G-C

Position:

• chr3-45923752-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024513.4(FYCO1):​c.4265C>G​(p.Thr1422Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
• Consequence: FYCO1 NM_024513.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3295893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FYCO1	NM_024513.4	c.4265C>G	p.Thr1422Arg	missense_variant	17/18	ENST00000296137.7	NP_078789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FYCO1	ENST00000296137.7	c.4265C>G	p.Thr1422Arg	missense_variant	17/18	1	NM_024513.4	ENSP00000296137.2
FYCO1	ENST00000433878.5	c.629C>G	p.Thr210Arg	missense_variant	5/7	2		ENSP00000388136.1
FYCO1	ENST00000438446.1	c.278C>G	p.Thr93Arg	missense_variant	5/6	5		ENSP00000398517.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0060	.;T;T
Eigen	Benign	0.019
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	.;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.025	D;D;T
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.98	.;D;.
Vest4		0.52
MutPred		0.40		.;Loss of glycosylation at T1422 (P = 0.0252);.;
MVP		0.44
MPC		0.59
ClinPred		0.73	D
GERP RS		2.2
Varity_R		0.057
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs35678722; hg19: chr3-45965244;