NM_000147.5:c.1160+1046A>C

Variant names:

• chr1-23847603-T-G
• rs10917431
• NM_000147.5:c.1160+1046A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000147.5(FUCA1):​c.1160+1046A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,054 control chromosomes in the GnomAD database, including 10,695 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (10695 hom., cov: 32)
• Consequence: FUCA1 NM_000147.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 10 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUCA1	NM_000147.5	MANE Select	c.1160+1046A>C		intron	N/A	NP_000138.2
	FUCA1	NR_174379.1		n.1338+1046A>C		intron	N/A
	FUCA1	NR_174380.1		n.1387+1046A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUCA1	ENST00000374479.4	TSL:1 MANE Select	c.1160+1046A>C		intron	N/A	ENSP00000363603.3

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55549 AN: 151934 Hom.: 10688 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.387

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.366 AC: 55592 AN: 152054 Hom.: 10695 Cov.: 32 AF XY: 0.363 AC XY: 26962 AN XY: 74318

African (AFR) AF: 0.227 AC: 9416 AN: 41490

American (AMR) AF: 0.363 AC: 5547 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1501 AN: 3466

East Asian (EAS) AF: 0.476 AC: 2457 AN: 5164

South Asian (SAS) AF: 0.289 AC: 1389 AN: 4814

European-Finnish (FIN) AF: 0.436 AC: 4613 AN: 10578

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29333 AN: 67966

Other (OTH) AF: 0.393 AC: 827 AN: 2106

Alfa AF: 0.402 Hom.: 32694

Bravo AF: 0.355

Asia WGS AF: 0.367 AC: 1278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.76
PhyloP100		0.31
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: rs10917431; hg19: chr1-24174093; COSMIC: COSV65698845;