rs145035679

Variant names:

• chr19-5831623-G-T
• rs145035679
• NM_000150.4:c.945C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_000150.4(FUT6):​c.945C>A​(p.Tyr315*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00981 in 1,613,814 control chromosomes in the GnomAD database, including 375 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0085 (24 hom., cov: 31)
  • Exomes 𝑓: 0.010 (351 hom.)
• Consequence: FUT6 NM_000150.4 stop_gained
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 2.74
• Publications: 15 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 -9 ACMG points.

• BP6: Variant 19-5831623-G-T is Benign according to our data. Variant chr19-5831623-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 225367.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0565 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.945C>A	p.Tyr315*	stop_gained	Exon 3 of 3	NP_000141.1	P51993-1
	FUT6	NM_001040701.2		c.945C>A	p.Tyr315*	stop_gained	Exon 2 of 2	NP_001035791.1	P51993-1
	FUT6	NM_001369502.1		c.945C>A	p.Tyr315*	stop_gained	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.945C>A	p.Tyr315*	stop_gained	Exon 3 of 3	ENSP00000313398.4	P51993-1
	FUT6	ENST00000592563.1	TSL:1	c.945C>A	p.Tyr315*	stop_gained	Exon 1 of 2	ENSP00000466016.1	P51993-2
	FUT6	ENST00000286955.5	TSL:1	c.945C>A	p.Tyr315*	stop_gained	Exon 2 of 2	ENSP00000286955.5	P51993-1

Frequencies

GnomAD3 genomes AF: 0.00848 AC: 1291 AN: 152196 Hom.: 24 Cov.: 31

Gnomad AFR AF: 0.00309

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00525

Gnomad OTH AF: 0.00957

GnomAD2 exomes AF: 0.0174 AC: 4370 AN: 251054 AF XY: 0.0196

Gnomad AFR exome AF: 0.00291

Gnomad AMR exome AF: 0.00541

Gnomad ASJ exome AF: 0.0248

Gnomad EAS exome AF: 0.0697

Gnomad FIN exome AF: 0.00106

Gnomad NFE exome AF: 0.00592

Gnomad OTH exome AF: 0.0149

GnomAD4 exome AF: 0.00995 AC: 14546 AN: 1461500 Hom.: 351 Cov.: 31 AF XY: 0.0115 AC XY: 8355 AN XY: 727068

African (AFR) AF: 0.00224 AC: 75 AN: 33474

American (AMR) AF: 0.00541 AC: 242 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 660 AN: 26128

East Asian (EAS) AF: 0.0488 AC: 1936 AN: 39694

South Asian (SAS) AF: 0.0561 AC: 4842 AN: 86240

European-Finnish (FIN) AF: 0.00112 AC: 60 AN: 53370

Middle Eastern (MID) AF: 0.0148 AC: 82 AN: 5554

European-Non Finnish (NFE) AF: 0.00501 AC: 5576 AN: 1111962

Other (OTH) AF: 0.0178 AC: 1073 AN: 60358

GnomAD4 genome AF: 0.00846 AC: 1289 AN: 152314 Hom.: 24 Cov.: 31 AF XY: 0.00904 AC XY: 673 AN XY: 74478

African (AFR) AF: 0.00308 AC: 128 AN: 41580

American (AMR) AF: 0.00634 AC: 97 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3470

East Asian (EAS) AF: 0.0620 AC: 321 AN: 5174

South Asian (SAS) AF: 0.0531 AC: 256 AN: 4818

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00525 AC: 357 AN: 68028

Other (OTH) AF: 0.00947 AC: 20 AN: 2112

Alfa AF: 0.00992 Hom.: 2

Bravo AF: 0.00829

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.00675 AC: 58

ExAC AF: 0.0176 AC: 2133

EpiCase AF: 0.00758

EpiControl AF: 0.00729

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	Fucosyltransferase 6 deficiency (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.30
Eigen_PC	Benign	-0.0017
FATHMM_MKL	Uncertain	0.96	D
PhyloP100		2.7
Vest4		0.71
GERP RS		3.1
Mutation Taster		=113/87	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: rs145035679; hg19: chr19-5831634; COSMIC: COSV54607469; COSMIC: COSV54607469;