rs7652331

Variant names:

• chr3-45921260-T-C
• rs7652331
• NM_024513.4:c.*505A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-45921260-T-C
• chr3-45921260-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024513.4(FYCO1):​c.*505A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 210,050 control chromosomes in the GnomAD database, including 57,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43721 hom., cov: 33)
  • Exomes 𝑓: 0.68 (14079 hom.)
• Consequence: FYCO1 NM_024513.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.16
• Publications: 36 publications found

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 Gene-Disease associations (from GenCC):

• cataract 18

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 3-45921260-T-C is Benign according to our data. Variant chr3-45921260-T-C is described in ClinVar as Benign. ClinVar VariationId is 345484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024513.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYCO1	NM_024513.4	MANE Select	c.*505A>G		3_prime_UTR	Exon 18 of 18	NP_078789.2	Q9BQS8-1
	FYCO1	NM_001386421.1		c.*505A>G		3_prime_UTR	Exon 19 of 19	NP_001373350.1	Q9BQS8-1
	FYCO1	NM_001386422.1		c.*505A>G		3_prime_UTR	Exon 18 of 18	NP_001373351.1	Q9BQS8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYCO1	ENST00000296137.7	TSL:1 MANE Select	c.*505A>G		3_prime_UTR	Exon 18 of 18	ENSP00000296137.2	Q9BQS8-1
	FYCO1	ENST00000874259.1		c.*505A>G		3_prime_UTR	Exon 19 of 19	ENSP00000544318.1
	FYCO1	ENST00000965269.1		c.*505A>G		3_prime_UTR	Exon 18 of 18	ENSP00000635328.1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113453 AN: 152100 Hom.: 43658 Cov.: 33

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.753

GnomAD4 exome AF: 0.683 AC: 39525 AN: 57832 Hom.: 14079 Cov.: 0 AF XY: 0.677 AC XY: 20423 AN XY: 30162

African (AFR) AF: 0.911 AC: 1930 AN: 2118

American (AMR) AF: 0.828 AC: 3116 AN: 3762

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 819 AN: 1260

East Asian (EAS) AF: 0.998 AC: 3847 AN: 3856

South Asian (SAS) AF: 0.562 AC: 3884 AN: 6910

European-Finnish (FIN) AF: 0.657 AC: 1267 AN: 1928

Middle Eastern (MID) AF: 0.712 AC: 141 AN: 198

European-Non Finnish (NFE) AF: 0.645 AC: 22546 AN: 34934

Other (OTH) AF: 0.689 AC: 1975 AN: 2866

GnomAD4 genome AF: 0.746 AC: 113579 AN: 152218 Hom.: 43721 Cov.: 33 AF XY: 0.744 AC XY: 55368 AN XY: 74418

African (AFR) AF: 0.908 AC: 37758 AN: 41568

American (AMR) AF: 0.822 AC: 12576 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2306 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5154 AN: 5176

South Asian (SAS) AF: 0.575 AC: 2772 AN: 4822

European-Finnish (FIN) AF: 0.636 AC: 6727 AN: 10570

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44145 AN: 67982

Other (OTH) AF: 0.754 AC: 1596 AN: 2116

Alfa AF: 0.704 Hom.: 72373

Bravo AF: 0.775

Asia WGS AF: 0.792 AC: 2753 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cataract 18 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.077
DANN	Benign	0.26
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7652331; hg19: chr3-45962752;