19-48750654-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384359.1(FUT1):c.628C>A(p.Arg210Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FUT1 NM_001384359.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

Genes affected

FUT1 (HGNC:4012): (fucosyltransferase 1 (H blood group)) This gene encodes a Golgi stack membrane protein that is involved in the creation of a precursor of the H antigen, which is required for the final step in the synthesis of soluble A and B antigens. This is one of two genes encoding the galactoside 2-L-fucosyltransferase enzyme. Mutations in this gene are a cause of the H-Bombay blood group. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1888493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUT1	NM_001384359.1	c.628C>A	p.Arg210Ser	missense_variant	2/2	ENST00000645652.2
FUT1	NM_000148.4	c.628C>A	p.Arg210Ser	missense_variant	4/4
FUT1	NM_001329877.1	c.628C>A	p.Arg210Ser	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUT1	ENST00000645652.2	c.628C>A	p.Arg210Ser	missense_variant	2/2		NM_001384359.1	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460366 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726522

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000192

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2022

The c.628C>A (p.R210S) alteration is located in exon 4 (coding exon 1) of the FUT1 gene. This alteration results from a C to A substitution at nucleotide position 628, causing the arginine (R) at amino acid position 210 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.069	D
BayesDel_noAF	Benign	-0.14
Cadd	Benign	19
Dann	Benign	0.92
DEOGEN2	Benign	0.059	T;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.14	N
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
Polyphen		0.43	B;B
Vest4		0.17
MutPred		0.52		Loss of MoRF binding (P = 0.0215);Loss of MoRF binding (P = 0.0215);
MVP		0.92
MPC		0.68
ClinPred		0.45	T
GERP RS		2.3
Varity_R		0.068
gMVP		0.90

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: rs775020226; hg19: chr19-49253911;