rs13069079

Variant names:

• chr3-45959378-G-A
• rs13069079
• NM_024513.4:c.3587+15C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-45959378-G-A
• chr3-45959378-G-T

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.3587+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,613,428 control chromosomes in the GnomAD database, including 14,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (1011 hom., cov: 33)
  • Exomes 𝑓: 0.12 (13031 hom.)
• Consequence: FYCO1 NM_024513.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.800
• Publications: 12 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=-0.96).
• BP6: Variant 3-45959378-G-A is Benign according to our data. Variant chr3-45959378-G-A is described in ClinVar as Benign. ClinVar VariationId is 261732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 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.3587+15C>T		intron	N/A	NP_078789.2	Q9BQS8-1
	FYCO1	NM_001386421.1		c.3587+15C>T		intron	N/A	NP_001373350.1	Q9BQS8-1
	FYCO1	NM_001386422.1		c.3587+15C>T		intron	N/A	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.3587+15C>T		intron	N/A	ENSP00000296137.2	Q9BQS8-1
	FYCO1	ENST00000874259.1		c.3587+15C>T		intron	N/A	ENSP00000544318.1
	FYCO1	ENST00000965269.1		c.3587+15C>T		intron	N/A	ENSP00000635328.1

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13559 AN: 152098 Hom.: 1013 Cov.: 33

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.0664

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0919

GnomAD2 exomes AF: 0.126 AC: 31461 AN: 249376 AF XY: 0.141

Gnomad AFR exome AF: 0.0166

Gnomad AMR exome AF: 0.0641

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.00256

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.116 AC: 169272 AN: 1461212 Hom.: 13031 Cov.: 33 AF XY: 0.124 AC XY: 90334 AN XY: 726884

African (AFR) AF: 0.0160 AC: 534 AN: 33470

American (AMR) AF: 0.0655 AC: 2929 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 4717 AN: 26134

East Asian (EAS) AF: 0.00204 AC: 81 AN: 39700

South Asian (SAS) AF: 0.343 AC: 29563 AN: 86250

European-Finnish (FIN) AF: 0.144 AC: 7620 AN: 52986

Middle Eastern (MID) AF: 0.189 AC: 1090 AN: 5766

European-Non Finnish (NFE) AF: 0.104 AC: 115616 AN: 1111814

Other (OTH) AF: 0.118 AC: 7122 AN: 60370

GnomAD4 genome AF: 0.0890 AC: 13550 AN: 152216 Hom.: 1011 Cov.: 33 AF XY: 0.0950 AC XY: 7069 AN XY: 74420

African (AFR) AF: 0.0177 AC: 736 AN: 41546

American (AMR) AF: 0.0662 AC: 1013 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 632 AN: 3472

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5164

South Asian (SAS) AF: 0.350 AC: 1692 AN: 4828

European-Finnish (FIN) AF: 0.145 AC: 1539 AN: 10588

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7466 AN: 68000

Other (OTH) AF: 0.0928 AC: 196 AN: 2112

Alfa AF: 0.121 Hom.: 824

Bravo AF: 0.0722

Asia WGS AF: 0.172 AC: 599 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Cataract 18 (3)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.18
DANN	Benign	0.40
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13069079; hg19: chr3-46000870;