rs13551

Variant names:

• chr1-23854472-T-C
• rs13551
• NM_000147.5:c.857A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000147.5(FUCA1):​c.857A>G​(p.Gln286Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,613,656 control chromosomes in the GnomAD database, including 81,648 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q286Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.27 (6033 hom., cov: 32)
  • Exomes 𝑓: 0.32 (75615 hom.)
• Consequence: FUCA1 NM_000147.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.687
• Publications: 40 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.5064092E-4).
• BP6: Variant 1-23854472-T-C is Benign according to our data. Variant chr1-23854472-T-C is described in ClinVar as Benign. ClinVar VariationId is 691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUCA1	NM_000147.5	MANE Select	c.857A>G	p.Gln286Arg	missense	Exon 5 of 8	NP_000138.2	P04066
	FUCA1	NR_174379.1		n.1035A>G		non_coding_transcript_exon	Exon 5 of 8
	FUCA1	NR_174380.1		n.1084A>G		non_coding_transcript_exon	Exon 6 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUCA1	ENST00000374479.4	TSL:1 MANE Select	c.857A>G	p.Gln286Arg	missense	Exon 5 of 8	ENSP00000363603.3	P04066
	FUCA1	ENST00000965619.1		c.857A>G	p.Gln286Arg	missense	Exon 5 of 8	ENSP00000635678.1
	FUCA1	ENST00000881205.1		c.768+5326A>G		intron	N/A	ENSP00000551264.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40805 AN: 152038 Hom.: 6032 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.288

GnomAD2 exomes AF: 0.279 AC: 70217 AN: 251490 AF XY: 0.278

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.204

Gnomad ASJ exome AF: 0.301

Gnomad EAS exome AF: 0.265

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.296

GnomAD4 exome AF: 0.315 AC: 460378 AN: 1461500 Hom.: 75615 Cov.: 36 AF XY: 0.311 AC XY: 226103 AN XY: 727112

African (AFR) AF: 0.136 AC: 4553 AN: 33478

American (AMR) AF: 0.207 AC: 9274 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 7975 AN: 26136

East Asian (EAS) AF: 0.253 AC: 10056 AN: 39698

South Asian (SAS) AF: 0.155 AC: 13377 AN: 86256

European-Finnish (FIN) AF: 0.393 AC: 20977 AN: 53420

Middle Eastern (MID) AF: 0.235 AC: 1357 AN: 5768

European-Non Finnish (NFE) AF: 0.337 AC: 374375 AN: 1111646

Other (OTH) AF: 0.305 AC: 18434 AN: 60374

GnomAD4 genome AF: 0.268 AC: 40816 AN: 152156 Hom.: 6033 Cov.: 32 AF XY: 0.266 AC XY: 19773 AN XY: 74378

African (AFR) AF: 0.145 AC: 6011 AN: 41538

American (AMR) AF: 0.239 AC: 3647 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3470

East Asian (EAS) AF: 0.264 AC: 1370 AN: 5182

South Asian (SAS) AF: 0.148 AC: 714 AN: 4832

European-Finnish (FIN) AF: 0.400 AC: 4217 AN: 10554

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22783 AN: 67988

Other (OTH) AF: 0.286 AC: 604 AN: 2112

Alfa AF: 0.304 Hom.: 17095

Bravo AF: 0.254

TwinsUK AF: 0.346 AC: 1283

ALSPAC AF: 0.331 AC: 1274

ESP6500AA AF: 0.146 AC: 643

ESP6500EA AF: 0.331 AC: 2845

ExAC AF: 0.279 AC: 33884

Asia WGS AF: 0.187 AC: 652 AN: 3478

EpiCase AF: 0.325

EpiControl AF: 0.315

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	Fucosidosis (2)
-	-	1	FU1/FU2 POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.00045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.24	N
PhyloP100		0.69
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.057
Sift	Benign	0.038	D
Sift4G	Benign	0.074	T
Polyphen		0.0010	B
Vest4		0.014
MPC		0.35
ClinPred		0.0057	T
GERP RS		3.6
Varity_R		0.093
gMVP		0.58
Mutation Taster		=99/1	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: rs13551; hg19: chr1-24180962; COSMIC: COSV65698861;