Variant 19-5866750-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002034.2(FUT5):c.976C>T(p.His326Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 150,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000032 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

FUT5
NM_002034.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.685

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03682947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT5	NM_002034.2 linkuse as main transcript	c.976C>T	p.His326Tyr	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.976C>T	p.His326Tyr	missense_variant	2/2	1	NM_002034.2	ENSP00000466880	P1
FUT5	ENST00000252675.6 linkuse as main transcript	c.976C>T	p.His326Tyr	missense_variant	1/1			ENSP00000252675	P1

Frequencies

GnomAD3 genomes

AF:

0.0000465

AC:

AN:

150630

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000982

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000640

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000415

AC:

AN:

216662

Hom.:

AF XY:

0.0000676

AC XY:

AN XY:

118304

show subpopulations

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 SAS exome

AF:

0.000318

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000318

AC:

AN:

1448066

Hom.:

Cov.:

AF XY:

0.0000417

AC XY:

AN XY:

719994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000517

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.0000465

AC:

AN:

150630

Hom.:

Cov.:

AF XY:

0.0000817

AC XY:

AN XY:

73484

show subpopulations

Gnomad4 AFR

AF:

0.0000982

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000640

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000333

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

Jun 16, 2023

The c.976C>T (p.H326Y) alteration is located in exon 2 (coding exon 1) of the FUT5 gene. This alteration results from a C to T substitution at nucleotide position 976, causing the histidine (H) at amino acid position 326 to be replaced by a tyrosine (Y). 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

Benign

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.1

DANN

Benign

0.58

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.37

T;.

M_CAP

Benign

0.0014

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.015

Sift

Benign

0.26

T;.

Sift4G

Benign

0.11

T;T

Vest4

0.13

MutPred

0.45

Gain of phosphorylation at H326 (P = 0.0582);Gain of phosphorylation at H326 (P = 0.0582);

MVP

0.19

MPC

0.61

ClinPred

0.025

GERP RS

-4.7

gMVP

0.35

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