19-48751247-G-T

Variant names:

• chr19-48751247-G-T
• rs2071699
• NM_001384359.1:c.35C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384359.1(FUT1):​c.35C>A​(p.Ala12Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A12V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FUT1 NM_001384359.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240
• Publications: 49 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16726097).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384359.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT1	NM_001384359.1	MANE Select	c.35C>A	p.Ala12Asp	missense	Exon 2 of 2	NP_001371288.1
	FUT1	NM_000148.4		c.35C>A	p.Ala12Asp	missense	Exon 4 of 4	NP_000139.1
	FUT1	NM_001329877.1		c.35C>A	p.Ala12Asp	missense	Exon 5 of 5	NP_001316806.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT1	ENST00000645652.2	MANE Select	c.35C>A	p.Ala12Asp	missense	Exon 2 of 2	ENSP00000494643.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.00074	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.024
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.27	T
Polyphen		0.61	P
Vest4		0.32
MutPred		0.51		Loss of catalytic residue at A12 (P = 0.069)
MVP		0.56
MPC		1.1
ClinPred		0.34	T
GERP RS		-1.3
Varity_R		0.30
gMVP		0.70
Mutation Taster		=90/10	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

Other links and lift over

dbSNP: rs2071699; hg19: chr19-49254504;