chr19-48750656-T-G

Variant names:

• chr19-48750656-T-G
• rs760165583
• NM_001384359.1:c.626A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384359.1(FUT1):​c.626A>C​(p.Asp209Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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: 0.0000027 (0 hom.)
• Consequence: FUT1 NM_001384359.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.35
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03938079).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT1	NM_001384359.1	MANE Select	c.626A>C	p.Asp209Ala	missense	Exon 2 of 2	NP_001371288.1	Q6IZA2
	FUT1	NM_000148.4		c.626A>C	p.Asp209Ala	missense	Exon 4 of 4	NP_000139.1	P19526
	FUT1	NM_001329877.1		c.626A>C	p.Asp209Ala	missense	Exon 5 of 5	NP_001316806.1	Q6IZA2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT1	ENST00000645652.2	MANE Select	c.626A>C	p.Asp209Ala	missense	Exon 2 of 2	ENSP00000494643.1	P19526
	FUT1	ENST00000927212.1		c.626A>C	p.Asp209Ala	missense	Exon 2 of 2	ENSP00000597271.1
	FUT1	ENST00000927213.1		c.626A>C	p.Asp209Ala	missense	Exon 2 of 2	ENSP00000597272.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 249008 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460436 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726546

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111926

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.037
DANN	Benign	0.72
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.039	T
MetaSVM	Uncertain	0.0013	D
MutationAssessor	Benign	-0.16	N
PhyloP100		-2.4
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.11
Sift	Benign	0.34	T
Sift4G	Benign	0.59	T
Polyphen		0.0010	B
Vest4		0.067
MutPred		0.35		Gain of methylation at R210 (P = 0.0392)
MVP		0.65
MPC		0.54
ClinPred		0.078	T
GERP RS		-6.5
Varity_R		0.032
gMVP		0.81
Mutation Taster		=89/11	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: rs760165583; hg19: chr19-49253913;