Genetic Variant FUCA1:p.Pro10Gln (chr1-23868258-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000147.5(FUCA1):c.29C>A(p.Pro10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,404,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P10R) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FUCA1
NM_000147.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.702

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09921241).

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>A	p.Pro10Gln	missense	Exon 1 of 8	NP_000138.2
FUCA1	NR_174379.1		n.33C>A		non_coding_transcript_exon	Exon 1 of 8
FUCA1	NR_174380.1		n.33C>A		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>A	p.Pro10Gln	missense	Exon 1 of 8	ENSP00000363603.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1404786

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

694228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32050

American (AMR)

AF:

0.00

AC:

AN:

37000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25234

East Asian (EAS)

AF:

0.00

AC:

AN:

36454

South Asian (SAS)

AF:

0.00

AC:

AN:

80510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5194

European-Non Finnish (NFE)

AF:

0.00000184

AC:

AN:

1084712

Other (OTH)

AF:

0.00

AC:

AN:

58232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.2

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.064

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.33

M_CAP

Benign

0.011

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

0.70

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.010

REVEL

Benign

0.030

Sift

Benign

0.065

Sift4G

Benign

0.32

Polyphen

0.27

Vest4

0.24

MutPred

0.28

Gain of MoRF binding (P = 0.0257)

MVP

0.22

MPC

0.41

ClinPred

0.26

GERP RS

-3.3

PromoterAI

-0.072

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.053

gMVP

0.39

Mutation Taster

=99/1

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over