rs3762001

Variant names:

• chr6-143501975-G-A
• rs3762001
• NM_032020.5:c.1111C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032020.5(FUCA2):​c.1111C>T​(p.His371Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,612,406 control chromosomes in the GnomAD database, including 37,759 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.20 (3150 hom., cov: 31)
  • Exomes 𝑓: 0.21 (34609 hom.)
• Consequence: FUCA2 NM_032020.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

Genes affected

FUCA2 (HGNC:4008): (alpha-L-fucosidase 2) This gene encodes a plasma alpha-L-fucosidase, which represents 10-20% of the total cellular fucosidase activity. The protein is a member of the glycosyl hydrolase 29 family, and catalyzes the hydrolysis of the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins. This enzyme is essential for Helicobacter pylori adhesion to human gastric cancer cells. [provided by RefSeq, Aug 2010]

VDAC1P8 (HGNC:37483): (voltage dependent anion channel 1 pseudogene 8)

ENSG00000278206 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01053381).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUCA2	NM_032020.5	c.1111C>T	p.His371Tyr	missense_variant	Exon 5 of 7	ENST00000002165.11	NP_114409.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUCA2	ENST00000002165.11	c.1111C>T	p.His371Tyr	missense_variant	Exon 5 of 7	1	NM_032020.5	ENSP00000002165.5

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30086 AN: 151788 Hom.: 3153 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.188

GnomAD3 exomes AF: 0.207 AC: 51901 AN: 251222 Hom.: 5770 AF XY: 0.209 AC XY: 28434 AN XY: 135774

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.182

Gnomad SAS exome AF: 0.187

Gnomad FIN exome AF: 0.284

Gnomad NFE exome AF: 0.222

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.215 AC: 313796 AN: 1460500 Hom.: 34609 Cov.: 33 AF XY: 0.215 AC XY: 156320 AN XY: 726552

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.198 AC: 30085 AN: 151906 Hom.: 3150 Cov.: 31 AF XY: 0.199 AC XY: 14783 AN XY: 74232

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.188

Alfa AF: 0.215 Hom.: 8346

Bravo AF: 0.186

TwinsUK AF: 0.222 AC: 823

ALSPAC AF: 0.219 AC: 845

ESP6500AA AF: 0.153 AC: 676

ESP6500EA AF: 0.225 AC: 1934

ExAC AF: 0.206 AC: 25051

Asia WGS AF: 0.174 AC: 604 AN: 3478

EpiCase AF: 0.219

EpiControl AF: 0.221

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.4
DANN	Benign	0.90
DEOGEN2	Benign	0.078	T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.70	T;T
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.095
Sift	Benign	0.14	T;T
Sift4G	Benign	0.90	T;T
Polyphen		0.0	B;B
Vest4		0.073
MPC		0.21
ClinPred		0.0023	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.079
gMVP		0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs3762001; hg19: chr6-143823112; COSMIC: COSV50019753; COSMIC: COSV50019753;