rs763175994

Variant names:

• chr11-94544449-T-G
• rs763175994
• NM_002033.4:c.316T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002033.4(FUT4):​c.316T>G​(p.Cys106Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000358 in 1,509,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: FUT4 NM_002033.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.28
• Publications: 0 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]

ACMG classification

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=0.036040872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUT4	NM_002033.4	c.316T>G	p.Cys106Gly	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.316T>G	p.Cys106Gly	missense_variant	Exon 1 of 1	6	NM_002033.4	ENSP00000351602.2
PIWIL4	ENST00000543336.5	n.-121+460T>G		intron_variant	Intron 1 of 13	2		ENSP00000444575.1

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151910 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000883

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000880 AC: 9 AN: 102236 AF XY: 0.000122

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000539

Gnomad OTH exome AF: 0.000657

GnomAD4 exome AF: 0.0000339 AC: 46 AN: 1357550 Hom.: 0 Cov.: 31 AF XY: 0.0000433 AC XY: 29 AN XY: 670228

African (AFR) AF: 0.00 AC: 0 AN: 27910

American (AMR) AF: 0.00 AC: 0 AN: 33690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24176

East Asian (EAS) AF: 0.00 AC: 0 AN: 31670

South Asian (SAS) AF: 0.000168 AC: 13 AN: 77242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33644

Middle Eastern (MID) AF: 0.000238 AC: 1 AN: 4198

European-Non Finnish (NFE) AF: 0.0000262 AC: 28 AN: 1068322

Other (OTH) AF: 0.0000705 AC: 4 AN: 56698

GnomAD4 genome AF: 0.0000527 AC: 8 AN: 151910 Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4 AN XY: 74210

African (AFR) AF: 0.0000242 AC: 1 AN: 41402

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5100

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

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

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67948

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000409 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.316T>G (p.C106G) alteration is located in exon 1 (coding exon 1) of the FUT4 gene. This alteration results from a T to G substitution at nucleotide position 316, causing the cysteine (C) at amino acid position 106 to be replaced by a glycine (G). 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	0.060
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.90
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
PhyloP100		-1.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.033
Sift	Benign	1.0	T
Sift4G	Benign	0.45	T
Polyphen		0.21	B
Vest4		0.028
MutPred		0.38		Loss of stability (P = 0.0029);
MVP		0.33
MPC		0.97
ClinPred		0.020	T
GERP RS		-0.47
Varity_R		0.068
gMVP		0.11
Mutation Taster		=99/1	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: rs763175994; hg19: chr11-94277615;