1-23868258-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000147.5(FUCA1):c.29C>G(p.Pro10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,556,742 control chromosomes in the GnomAD database, including 8,542 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P10P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.11 ( 964 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7578 hom. )

Consequence

FUCA1
NM_000147.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: 0.702

Publications

24 publications found

Variant links:

Genes affected

FUCA1 (HGNC:4006): (alpha-L-fucosidase 1) The protein encoded by this gene is a lysosomal enzyme involved in the degradation of fucose-containing glycoproteins and glycolipids. Mutations in this gene are associated with fucosidosis (FUCA1D), which is an autosomal recessive lysosomal storage disease. A pseudogene of this locus is present on chr 2.[provided by RefSeq, Oct 2009]

FUCA1 Gene-Disease associations (from GenCC):

fucosidosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Genomics England PanelApp, Ambry Genetics, ClinGen

FUCA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0044653714).

BP6

Variant 1-23868258-G-C is Benign according to our data. Variant chr1-23868258-G-C is described in ClinVar as Benign. ClinVar VariationId is 193053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000147.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FUCA1	NM_000147.5	MANE Select	c.29C>G	p.Pro10Arg	missense	Exon 1 of 8	NP_000138.2
FUCA1	NR_174379.1		n.33C>G		non_coding_transcript_exon	Exon 1 of 8
FUCA1	NR_174380.1		n.33C>G		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUCA1	ENST00000374479.4	TSL:1 MANE Select	c.29C>G	p.Pro10Arg	missense	Exon 1 of 8	ENSP00000363603.3

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16261

AN:

152106

Hom.:

954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.0362

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0959

Gnomad OTH

AF:

0.104

GnomAD2 exomes

AF:

0.108

AC:

16227

AN:

150532

AF XY:

0.108

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.0353

Gnomad NFE exome

AF:

0.0910

Gnomad OTH exome

AF:

0.0991

GnomAD4 exome

AF:

0.101

AC:

141225

AN:

1404520

Hom.:

7578

Cov.:

AF XY:

0.101

AC XY:

70129

AN XY:

694076

show subpopulations

African (AFR)

AF:

0.116

AC:

3713

AN:

32038

American (AMR)

AF:

0.118

AC:

4347

AN:

36990

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

3355

AN:

25230

East Asian (EAS)

AF:

0.175

AC:

6367

AN:

36444

South Asian (SAS)

AF:

0.124

AC:

10011

AN:

80492

European-Finnish (FIN)

AF:

0.0410

AC:

1863

AN:

45388

Middle Eastern (MID)

AF:

0.0660

AC:

343

AN:

5194

European-Non Finnish (NFE)

AF:

0.0967

AC:

104925

AN:

1084518

Other (OTH)

AF:

0.108

AC:

6301

AN:

58226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

7248

14496

21743

28991

36239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4060

8120

12180

16240

20300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.107

AC:

16316

AN:

152222

Hom.:

964

Cov.:

AF XY:

0.107

AC XY:

7933

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.119

AC:

4938

AN:

41540

American (AMR)

AF:

0.127

AC:

1946

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

477

AN:

3470

East Asian (EAS)

AF:

0.209

AC:

1076

AN:

5154

South Asian (SAS)

AF:

0.140

AC:

677

AN:

4826

European-Finnish (FIN)

AF:

0.0362

AC:

385

AN:

10624

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0959

AC:

6523

AN:

67990

Other (OTH)

AF:

0.112

AC:

237

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

771

1542

2312

3083

3854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0695

Hom.:

152

Bravo

AF:

0.112

TwinsUK

AF:

0.0839

AC:

311

ALSPAC

AF:

0.0926

AC:

357

ExAC

AF:

0.0587

AC:

6308

Asia WGS

AF:

0.182

AC:

631

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jun 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Dec 16, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

not specified

Benign:2

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 268/2178=12.3%

Jun 26, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Fucosidosis

Benign:2

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.4

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

0.70

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.15

REVEL

Benign

0.089

Sift

Benign

0.061

Sift4G

Benign

0.30

Polyphen

0.27

Vest4

0.079

MPC

0.40

ClinPred

0.015

GERP RS

-3.3

PromoterAI

-0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.063

gMVP

0.50

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over