19-48750666-G-T

Variant names:

• chr19-48750666-G-T
• rs762860495
• NM_001384359.1:c.616C>A

Variant summary

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

The NM_001384359.1(FUT1):​c.616C>A​(p.Arg206Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FUT1 NM_001384359.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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=0.114803046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT1	NM_001384359.1	c.616C>A	p.Arg206Ser	missense_variant	Exon 2 of 2	ENST00000645652.2	NP_001371288.1
FUT1	NM_000148.4	c.616C>A	p.Arg206Ser	missense_variant	Exon 4 of 4		NP_000139.1
FUT1	NM_001329877.1	c.616C>A	p.Arg206Ser	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.616C>A	p.Arg206Ser	missense_variant	Exon 2 of 2		NM_001384359.1	ENSP00000494643.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249326 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135252

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460598 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726628

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.060	T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.56	.;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Uncertain	-0.085	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	.;N
REVEL	Uncertain	0.32
Sift	Benign	0.13	.;T
Sift4G	Benign	0.49	.;T
Polyphen		0.61	P;P
Vest4		0.042
MutPred		0.43		Gain of relative solvent accessibility (P = 0.0098);Gain of relative solvent accessibility (P = 0.0098);
MVP		0.89
MPC		0.77
ClinPred		0.071	T
GERP RS		-2.2
Varity_R		0.10
gMVP		0.81

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: rs762860495; hg19: chr19-49253923;