11-94544177-G-C

Variant names:

• chr11-94544177-G-C
• rs1277768476
• NM_002033.4:c.44G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002033.4(FUT4):​c.44G>C​(p.Gly15Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,397,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: FUT4 NM_002033.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.658
• Publications: 1 publications found

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]

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]

ENSG00000304830 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.26069966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT4	NM_002033.4	c.44G>C	p.Gly15Ala	missense_variant	Exon 1 of 1	ENST00000358752.4	NP_002024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUT4	ENST00000358752.4	c.44G>C	p.Gly15Ala	missense_variant	Exon 1 of 1	6	NM_002033.4	ENSP00000351602.2
PIWIL4	ENST00000543336.5	n.-121+188G>C		intron_variant	Intron 1 of 13	2		ENSP00000444575.1
ENSG00000304830	ENST00000806516.1	n.-33C>G		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000478

GnomAD4 exome AF: 0.0000112 AC: 14 AN: 1245176 Hom.: 0 Cov.: 30 AF XY: 0.0000149 AC XY: 9 AN XY: 604856

African (AFR) AF: 0.000459 AC: 11 AN: 23960

American (AMR) AF: 0.00 AC: 0 AN: 11754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17170

East Asian (EAS) AF: 0.00 AC: 0 AN: 27892

South Asian (SAS) AF: 0.0000178 AC: 1 AN: 56136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3442

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1010226

Other (OTH) AF: 0.0000394 AC: 2 AN: 50808

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74344

African (AFR) AF: 0.0000724 AC: 3 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.44G>C (p.G15A) alteration is located in exon 1 (coding exon 1) of the FUT4 gene. This alteration results from a G to C substitution at nucleotide position 44, causing the glycine (G) at amino acid position 15 to be replaced by an alanine (A). 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	0.078
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.37	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.66
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.10
MutPred		0.072		Loss of loop (P = 0.0073);
MVP		0.59
MPC		1.8
ClinPred		0.62	D
GERP RS		3.1
PromoterAI		0.17	Neutral
Varity_R		0.19
gMVP		0.035
Mutation Taster		=91/9	polymorphism

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: rs1277768476; hg19: chr11-94277343;