NM_001384359.1:c.616C>T

Variant names:

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

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.616C>T​(p.Arg206Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,612,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: FUT1 NM_001384359.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0410
• Publications: 2 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=0.2631266).

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.616C>T	p.Arg206Cys	missense	Exon 2 of 2	NP_001371288.1	Q6IZA2
	FUT1	NM_000148.4		c.616C>T	p.Arg206Cys	missense	Exon 4 of 4	NP_000139.1	P19526
	FUT1	NM_001329877.1		c.616C>T	p.Arg206Cys	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.616C>T	p.Arg206Cys	missense	Exon 2 of 2	ENSP00000494643.1	P19526
	FUT1	ENST00000927212.1		c.616C>T	p.Arg206Cys	missense	Exon 2 of 2	ENSP00000597271.1
	FUT1	ENST00000927213.1		c.616C>T	p.Arg206Cys	missense	Exon 2 of 2	ENSP00000597272.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 249326 AF XY: 0.0000148

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000356

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1460598 Hom.: 0 Cov.: 33 AF XY: 0.0000275 AC XY: 20 AN XY: 726628

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

American (AMR) AF: 0.00 AC: 0 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: 52234

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

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1111946

Other (OTH) AF: 0.0000497 AC: 3 AN: 60372

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152232 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74372

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

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	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.052	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.041
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.33
Sift	Benign	0.030	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.15
MutPred		0.51		Loss of MoRF binding (P = 0.0024)
MVP		0.87
MPC		1.4
ClinPred		0.56	D
GERP RS		-2.2
Varity_R		0.12
gMVP		0.84
Mutation Taster		=97/3	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: rs762860495; hg19: chr19-49253923; COSMIC: COSV59568293; COSMIC: COSV59568293;