3-45968372-C-A

Position:

• chr3-45968372-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024513.4(FYCO1):​c.962G>T​(p.Gly321Val) 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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G321A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FYCO1 NM_024513.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06389138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FYCO1	NM_024513.4	c.962G>T	p.Gly321Val	missense_variant	8/18	ENST00000296137.7	NP_078789.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FYCO1	ENST00000296137.7	c.962G>T	p.Gly321Val	missense_variant	8/18	1	NM_024513.4	ENSP00000296137	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.0044	.;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	0.95	P;P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.21	N;N
REVEL	Benign	0.071
Sift	Benign	0.19	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.0	.;B
Vest4		0.12
MutPred		0.18		Loss of disorder (P = 0.0544);Loss of disorder (P = 0.0544);
MVP		0.17
MPC		0.21
ClinPred		0.11	T
GERP RS		3.8
Varity_R		0.042
gMVP		0.11

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: rs3733100; hg19: chr3-46009864;