rs11349487

Variant names:

• chr3-45918507-TA-T
• rs11349487
• NM_024513.4:c.*3257delT

Your query was ambiguous. Multiple possible variants found:

• chr3-45918507-TA-T
• chr3-45918507-TA-TAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024513.4(FYCO1):​c.*3257delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (13874 hom., cov: 0)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: FYCO1 NM_024513.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.06
• Publications: 2 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 -10 ACMG points.

• BP6: Variant 3-45918507-TA-T is Benign according to our data. Variant chr3-45918507-TA-T is described in ClinVar as Benign. ClinVar VariationId is 345443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 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.*3257delT		3_prime_UTR	Exon 18 of 18	NP_078789.2	Q9BQS8-1
	FYCO1	NM_001386421.1		c.*3257delT		3_prime_UTR	Exon 19 of 19	NP_001373350.1	Q9BQS8-1
	FYCO1	NM_001386422.1		c.*3257delT		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.*3257delT		3_prime_UTR	Exon 18 of 18	ENSP00000296137.2	Q9BQS8-1
	FYCO1	ENST00000874259.1		c.*3257delT		3_prime_UTR	Exon 19 of 19	ENSP00000544318.1
	FYCO1	ENST00000965269.1		c.*3257delT		3_prime_UTR	Exon 18 of 18	ENSP00000635328.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57206 AN: 151776 Hom.: 13838 Cov.: 0

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.377 AC: 57285 AN: 151894 Hom.: 13874 Cov.: 0 AF XY: 0.369 AC XY: 27437 AN XY: 74256

African (AFR) AF: 0.695 AC: 28729 AN: 41338

American (AMR) AF: 0.303 AC: 4631 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 906 AN: 3470

East Asian (EAS) AF: 0.348 AC: 1795 AN: 5158

South Asian (SAS) AF: 0.210 AC: 1007 AN: 4806

European-Finnish (FIN) AF: 0.200 AC: 2118 AN: 10574

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.253 AC: 17162 AN: 67956

Other (OTH) AF: 0.371 AC: 782 AN: 2110

Alfa AF: 0.323 Hom.: 1230

Bravo AF: 0.407

Asia WGS AF: 0.273 AC: 946 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Developmental cataract (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.1
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: rs11349487; hg19: chr3-45959999; COSMIC: COSV56113152; COSMIC: COSV56113152;