1-23868258-G-C

Position:

chr1-23868258-G-C

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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 links:

FUCA1 (HGNC:):

FUCA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUCA1	NM_000147.5 linkuse as main transcript	c.29C>G	p.Pro10Arg	missense_variant	1/8	ENST00000374479.4	NP_000138.2	P04066

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUCA1	ENST00000374479.4 linkuse as main transcript	c.29C>G	p.Pro10Arg	missense_variant	1/8	1	NM_000147.5	ENSP00000363603.3		P04066

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

GnomAD3 exomes

AF:

0.108

AC:

16227

AN:

150532

Hom.:

1011

AF XY:

0.108

AC XY:

8899

AN XY:

82572

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 SAS exome

AF:

0.127

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

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.175

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.0410

Gnomad4 NFE exome

AF:

0.0967

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.107

AC:

16316

AN:

152222

Hom.:

964

Cov.:

AF XY:

0.107

AC XY:

7933

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.209

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.0362

Gnomad4 NFE

AF:

0.0959

Gnomad4 OTH

AF:

0.112

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Uncertain significance, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 16, 2015	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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% -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 26, 2014	- -

Fucosidosis

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

8.4

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

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.063

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over