19-48750444-T-G

Variant names:

• chr19-48750444-T-G
• NM_001384359.1:c.838A>C

Variant summary

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

The NM_001384359.1(FUT1):​c.838A>C​(p.Thr280Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 6.8e-7 (0 hom.)
• Consequence: FUT1 NM_001384359.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.846

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=0.22037327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT1	NM_001384359.1	c.838A>C	p.Thr280Pro	missense_variant	Exon 2 of 2	ENST00000645652.2	NP_001371288.1
FUT1	NM_000148.4	c.838A>C	p.Thr280Pro	missense_variant	Exon 4 of 4		NP_000139.1
FUT1	NM_001329877.1	c.838A>C	p.Thr280Pro	missense_variant	Exon 5 of 5		NP_001316806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT1	ENST00000645652.2	c.838A>C	p.Thr280Pro	missense_variant	Exon 2 of 2		NM_001384359.1	ENSP00000494643.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

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: 0.00

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

Jun 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.838A>C (p.T280P) alteration is located in exon 4 (coding exon 1) of the FUT1 gene. This alteration results from a A to C substitution at nucleotide position 838, causing the threonine (T) at amino acid position 280 to be replaced by a proline (P). 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	0.31
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	6.4
DANN	Benign	0.95
DEOGEN2	Benign	0.097	T;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.67	.;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	.;N
REVEL	Uncertain	0.33
Sift	Benign	0.055	.;T
Sift4G	Benign	0.10	.;T
Polyphen		0.68	P;P
Vest4		0.11
MutPred		0.40		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.86
MPC		0.73
ClinPred		0.15	T
GERP RS		-3.3
Varity_R		0.40
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-49253701;