Genetic Variant FUT6:p.Gln230Lys (chr19-5831880-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000150.4(FUT6):c.688C>A(p.Gln230Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,613,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

FUT6
NM_000150.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.74

Publications

10 publications found

Variant links:

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

FUT6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018610537).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FUT6	NM_000150.4	MANE Select	c.688C>A	p.Gln230Lys	missense	Exon 3 of 3	NP_000141.1	P51993-1
FUT6	NM_001040701.2		c.688C>A	p.Gln230Lys	missense	Exon 2 of 2	NP_001035791.1	P51993-1
FUT6	NM_001369502.1		c.688C>A	p.Gln230Lys	missense	Exon 4 of 4	NP_001356431.1	P51993-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FUT6	ENST00000318336.10	TSL:2 MANE Select	c.688C>A	p.Gln230Lys	missense	Exon 3 of 3	ENSP00000313398.4	P51993-1
FUT6	ENST00000592563.1	TSL:1	c.688C>A	p.Gln230Lys	missense	Exon 1 of 2	ENSP00000466016.1	P51993-2
FUT6	ENST00000286955.5	TSL:1	c.688C>A	p.Gln230Lys	missense	Exon 2 of 2	ENSP00000286955.5	P51993-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000597

AC:

AN:

251174

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.000115

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000169

AC:

247

AN:

1461384

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

122

AN XY:

726950

show subpopulations

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

African (AFR)

AF:

0.0000299

AC:

AN:

33468

American (AMR)

AF:

0.0000447

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000465

AC:

AN:

86090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000209

AC:

232

AN:

1111744

Other (OTH)

AF:

0.000116

AC:

AN:

60372

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.352

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000190

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41542

American (AMR)

AF:

0.000327

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000415

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.0060

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0044

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.16

M_CAP

Benign

0.0041

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.20

PhyloP100

-4.7

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.11

REVEL

Benign

0.044

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.090

MVP

0.15

MPC

0.47

ClinPred

0.056

GERP RS

-3.5

Varity_R

0.084

gMVP

0.12

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over