rs61996282

Variant names:

• chr1-23868280-C-A
• rs61996282
• NM_000147.5:c.7G>T
• FUCA1 p.Ala3Ser

Your query was ambiguous. Multiple possible variants found:

• chr1-23868280-C-A
• chr1-23868280-C-G
• chr1-23868280-C-T

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.7G>T​(p.Ala3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,512 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FUCA1 NM_000147.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.15
• Publications: 4 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: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P

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 (MetaRNN=0.040700674).

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.7G>T	p.Ala3Ser	missense	Exon 1 of 8	NP_000138.2	P04066
	FUCA1	NR_174379.1		n.11G>T		non_coding_transcript_exon	Exon 1 of 8
	FUCA1	NR_174380.1		n.11G>T		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUCA1	ENST00000374479.4	TSL:1 MANE Select	c.7G>T	p.Ala3Ser	missense	Exon 1 of 8	ENSP00000363603.3	P04066
	FUCA1	ENST00000965619.1		c.7G>T	p.Ala3Ser	missense	Exon 1 of 8	ENSP00000635678.1
	FUCA1	ENST00000881205.1		c.7G>T	p.Ala3Ser	missense	Exon 1 of 7	ENSP00000551264.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000704 AC: 1 AN: 142052 AF XY: 0.0000129

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397512 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 690166

African (AFR) AF: 0.00 AC: 0 AN: 31856

American (AMR) AF: 0.00 AC: 0 AN: 36438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25206

East Asian (EAS) AF: 0.00 AC: 0 AN: 36260

South Asian (SAS) AF: 0.00 AC: 0 AN: 79974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4834

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1082238

Other (OTH) AF: 0.00 AC: 0 AN: 58008

GnomAD4 genome Cov.: 32

Alfa AF: 0.000202 Hom.: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.026
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-2.2
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.047
Sift	Benign	0.23	T
Sift4G	Benign	0.22	T
PromoterAI		0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.060
gMVP		0.21
Mutation Taster		=93/7	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs61996282;

hg19: chr1-24194770;