Variant 19-5866719-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_002034.2(FUT5):c.1007G>T(p.Arg336Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,456,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FUT5
NM_002034.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

FUT5 (HGNC:4016): (fucosyltransferase 5) Enables 3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity and 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity. Involved in ceramide metabolic process and oligosaccharide metabolic process. Predicted to be located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

FUT5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT5	NM_002034.2 linkuse as main transcript	c.1007G>T	p.Arg336Leu	missense_variant	2/2	ENST00000588525.1	NP_002025.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT5	ENST00000588525.1 linkuse as main transcript	c.1007G>T	p.Arg336Leu	missense_variant	2/2	1	NM_002034.2	ENSP00000466880	P1
FUT5	ENST00000252675.6 linkuse as main transcript	c.1007G>T	p.Arg336Leu	missense_variant	1/1			ENSP00000252675	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150972

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000489

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000823

AC:

AN:

243160

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000589

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000481

AC:

AN:

1456522

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

724490

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000453

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000331

AC:

AN:

150972

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73638

show subpopulations

Gnomad4 AFR

AF:

0.0000489

Gnomad4 AMR

AF:

0.000199

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000159

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.1007G>T (p.R336L) alteration is located in exon 2 (coding exon 1) of the FUT5 gene. This alteration results from a G to T substitution at nucleotide position 1007, causing the arginine (R) at amino acid position 336 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.14

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.84

T;.

M_CAP

Benign

0.017

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Benign

-0.44

MutationTaster

Benign

0.75

D;D

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-6.8

D;.

REVEL

Benign

0.22

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.0030

D;D

Vest4

0.44

MutPred

0.92

Loss of MoRF binding (P = 0.0205);Loss of MoRF binding (P = 0.0205);

MVP

0.57

MPC

1.6

ClinPred

0.97

GERP RS

2.3

gMVP

0.75

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over