chr19-48750791-A-T

Position:

• chr19-48750791-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001384359.1(FUT1):​c.491T>A​(p.Leu164His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FUT1 NM_001384359.1 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.64

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.989
• PP5: Variant 19-48750791-A-T is Pathogenic according to our data. Variant chr19-48750791-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 12140.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT1	NM_001384359.1	c.491T>A	p.Leu164His	missense_variant	2/2	ENST00000645652.2	NP_001371288.1
FUT1	NM_000148.4	c.491T>A	p.Leu164His	missense_variant	4/4		NP_000139.1
FUT1	NM_001329877.1	c.491T>A	p.Leu164His	missense_variant	5/5		NP_001316806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT1	ENST00000645652.2	c.491T>A	p.Leu164His	missense_variant	2/2		NM_001384359.1	ENSP00000494643	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Para-Bombay phenotype Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 21, 1994

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.32	T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	.;T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Pathogenic	3.1	M;M
MutationTaster	Benign	0.34	A
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.7	.;D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0020	.;D
Polyphen		1.0	D;D
Vest4		0.88
MutPred		0.92		Gain of methylation at K163 (P = 0.0382);Gain of methylation at K163 (P = 0.0382);
MVP		0.99
MPC		1.5
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.67
gMVP		0.99

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: rs104894687; hg19: chr19-49254048;