rs17855739

Variant names:

• chr19-5831829-C-T
• rs17855739
• NM_000150.4:c.739G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-5831829-C-T
• chr19-5831829-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000150.4(FUT6):​c.739G>A​(p.Glu247Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 1,613,460 control chromosomes in the GnomAD database, including 5,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1889 hom., cov: 31)
  • Exomes 𝑓: 0.056 (3983 hom.)
• Consequence: FUT6 NM_000150.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1
• Conservation: PhyloP100: 2.27
• Publications: 32 publications found

Genes affected

FUT6 (HGNC:4017): (fucosyltransferase 6) The protein encoded by this gene is a Golgi stack membrane protein that is involved in the creation of sialyl-Lewis X, an E-selectin ligand. Mutations in this gene are a cause of fucosyltransferase-6 deficiency. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

FUT6 Gene-Disease associations (from GenCC):

• fucosyltransferase 6 deficiency

  Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040969253).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000150.4. 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
	FUT6	NM_000150.4	MANE Select	c.739G>A	p.Glu247Lys	missense	Exon 3 of 3	NP_000141.1	P51993-1
	FUT6	NM_001040701.2		c.739G>A	p.Glu247Lys	missense	Exon 2 of 2	NP_001035791.1	P51993-1
	FUT6	NM_001369502.1		c.739G>A	p.Glu247Lys	missense	Exon 4 of 4	NP_001356431.1	P51993-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUT6	ENST00000318336.10	TSL:2 MANE Select	c.739G>A	p.Glu247Lys	missense	Exon 3 of 3	ENSP00000313398.4	P51993-1
	FUT6	ENST00000592563.1	TSL:1	c.739G>A	p.Glu247Lys	missense	Exon 1 of 2	ENSP00000466016.1	P51993-2
	FUT6	ENST00000286955.5	TSL:1	c.739G>A	p.Glu247Lys	missense	Exon 2 of 2	ENSP00000286955.5	P51993-1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17761 AN: 151696 Hom.: 1884 Cov.: 31

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.0775 AC: 19475 AN: 251182 AF XY: 0.0776

Gnomad AFR exome AF: 0.301

Gnomad AMR exome AF: 0.0419

Gnomad ASJ exome AF: 0.0649

Gnomad EAS exome AF: 0.103

Gnomad FIN exome AF: 0.0277

Gnomad NFE exome AF: 0.0428

Gnomad OTH exome AF: 0.0643

GnomAD4 exome AF: 0.0564 AC: 82396 AN: 1461646 Hom.: 3983 Cov.: 82 AF XY: 0.0584 AC XY: 42488 AN XY: 727132

African (AFR) AF: 0.301 AC: 10065 AN: 33462

American (AMR) AF: 0.0445 AC: 1989 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 1769 AN: 26132

East Asian (EAS) AF: 0.0715 AC: 2837 AN: 39700

South Asian (SAS) AF: 0.148 AC: 12723 AN: 86250

European-Finnish (FIN) AF: 0.0294 AC: 1569 AN: 53408

Middle Eastern (MID) AF: 0.0623 AC: 359 AN: 5762

European-Non Finnish (NFE) AF: 0.0420 AC: 46659 AN: 1111842

Other (OTH) AF: 0.0733 AC: 4426 AN: 60374

GnomAD4 genome AF: 0.117 AC: 17806 AN: 151814 Hom.: 1889 Cov.: 31 AF XY: 0.116 AC XY: 8605 AN XY: 74184

African (AFR) AF: 0.294 AC: 12117 AN: 41238

American (AMR) AF: 0.0648 AC: 991 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 230 AN: 3470

East Asian (EAS) AF: 0.103 AC: 530 AN: 5150

South Asian (SAS) AF: 0.137 AC: 655 AN: 4780

European-Finnish (FIN) AF: 0.0290 AC: 307 AN: 10598

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0400 AC: 2720 AN: 67978

Other (OTH) AF: 0.107 AC: 226 AN: 2108

Alfa AF: 0.0609 Hom.: 563

Bravo AF: 0.127

ESP6500AA AF: 0.289 AC: 1273

ESP6500EA AF: 0.0453 AC: 389

ExAC AF: 0.0833 AC: 10117

Asia WGS AF: 0.188 AC: 652 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Fucosyltransferase 6 deficiency (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Uncertain	0.070
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.36
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	4.2	H
PhyloP100		2.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.015	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.92	P
Vest4		0.38
MPC		0.58
ClinPred		0.074	T
GERP RS		2.0
Varity_R		0.71
gMVP		0.78
Mutation Taster		=100/0	polymorphism (auto)

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: rs17855739; hg19: chr19-5831840; COSMIC: COSV54605646; COSMIC: COSV54605646;