1-23845807-C-T

Variant names:

• chr1-23845807-C-T
• rs1639125891
• NM_000147.5:c.1309G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000147.5(FUCA1):​c.1309G>A​(p.Asp437Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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. D437H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FUCA1 NM_000147.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051249564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUCA1	NM_000147.5	c.1309G>A	p.Asp437Asn	missense_variant	Exon 8 of 8	ENST00000374479.4	NP_000138.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUCA1	ENST00000374479.4	c.1309G>A	p.Asp437Asn	missense_variant	Exon 8 of 8	1	NM_000147.5	ENSP00000363603.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.21
DANN	Benign	0.19
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.76	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.047
Sift	Benign	0.87	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.096
MutPred		0.27		Loss of ubiquitination at K438 (P = 0.0642);
MVP		0.21
MPC		0.31
ClinPred		0.026	T
GERP RS		-3.0
Varity_R		0.029
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs1639125891; hg19: chr1-24172297;