Genetic Variant NM_002033.4:c.40G>A (chr11-94544173-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002033.4(FUT4):c.40G>A(p.Ala14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,241,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A14S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

FUT4
NM_002033.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.794

Publications

0 publications found

Variant links:

Genes affected

FUT4 (HGNC:4015): (fucosyltransferase 4) The product of this gene transfers fucose to N-acetyllactosamine polysaccharides to generate fucosylated carbohydrate structures. It catalyzes the synthesis of the non-sialylated antigen, Lewis x (CD15). [provided by RefSeq, Jan 2009]

FUT4 links:

PIWIL4 (HGNC:18444): (piwi like RNA-mediated gene silencing 4) PIWIL4 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).[supplied by OMIM, Mar 2008]

PIWIL4 links:

ENSG00000304830 (HGNC:):

ENSG00000304830 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03828603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT4	NM_002033.4 link	c.40G>A	p.Ala14Thr	missense_variant	Exon 1 of 1	ENST00000358752.4	NP_002024.1	P22083-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FUT4	ENST00000358752.4 link	c.40G>A	p.Ala14Thr	missense_variant	Exon 1 of 1	6	NM_002033.4	ENSP00000351602.2	P22083-1
PIWIL4	ENST00000543336.5 link	n.-121+184G>A		intron_variant	Intron 1 of 13	2		ENSP00000444575.1	Q7Z3Z4-3
ENSG00000304830	ENST00000806516.1 link	n.-29C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000161

AC:

AN:

1241290

Hom.:

Cov.:

AF XY:

0.00000166

AC XY:

AN XY:

602504

show subpopulations

African (AFR)

AF:

0.0000419

AC:

AN:

23886

American (AMR)

AF:

0.00

AC:

AN:

11288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17116

East Asian (EAS)

AF:

0.00

AC:

AN:

27762

South Asian (SAS)

AF:

0.00

AC:

AN:

55636

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3426

European-Non Finnish (NFE)

AF:

9.92e-7

AC:

AN:

1007816

Other (OTH)

AF:

0.00

AC:

AN:

50668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.10

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.064

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.33

M_CAP

Benign

0.026

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.79

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.45

REVEL

Benign

0.049

Sift

Benign

0.32

Sift4G

Pathogenic

0.0

Polyphen

0.0060

Vest4

0.021

MutPred

0.099

Gain of phosphorylation at A14 (P = 0.0205);

MVP

0.23

MPC

0.76

ClinPred

0.17

GERP RS

-5.5

PromoterAI

-0.23

Neutral

(source)

Varity_R

0.038

gMVP

0.031

Mutation Taster

=99/1

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

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NM_002033.4:c.40G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over