chr1-23845429-G-T

Variant names:

• chr1-23845429-G-T
• rs886046324
• NM_000147.5:c.*286C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000147.5(FUCA1):​c.*286C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 302,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: FUCA1 NM_000147.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0240
• Publications: 0 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), G2P, Ambry Genetics, ClinGen, Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUCA1	NM_000147.5	MANE Select	c.*286C>A		3_prime_UTR	Exon 8 of 8	NP_000138.2	P04066
	FUCA1	NR_174379.1		n.1865C>A		non_coding_transcript_exon	Exon 8 of 8
	FUCA1	NR_174380.1		n.1914C>A		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUCA1	ENST00000374479.4	TSL:1 MANE Select	c.*286C>A		3_prime_UTR	Exon 8 of 8	ENSP00000363603.3	P04066
	FUCA1	ENST00000965619.1		c.*286C>A		3_prime_UTR	Exon 8 of 8	ENSP00000635678.1
	FUCA1	ENST00000881205.1		c.*286C>A		3_prime_UTR	Exon 7 of 7	ENSP00000551264.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000166 AC: 5 AN: 302048 Hom.: 0 Cov.: 2 AF XY: 0.0000307 AC XY: 5 AN XY: 162754

African (AFR) AF: 0.00 AC: 0 AN: 8820

American (AMR) AF: 0.00 AC: 0 AN: 13790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8658

East Asian (EAS) AF: 0.00 AC: 0 AN: 16992

South Asian (SAS) AF: 0.0000937 AC: 4 AN: 42690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1220

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 178778

Other (OTH) AF: 0.0000607 AC: 1 AN: 16480

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Fucosidosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.69
PhyloP100		-0.024
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs886046324; hg19: chr1-24171919;