11-94544612-G-A

Position:

• chr11-94544612-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002033.4(FUT4):​c.479G>A​(p.Gly160Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FUT4 NM_002033.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT4	NM_002033.4	c.479G>A	p.Gly160Asp	missense_variant	1/1	ENST00000358752.4	NP_002024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUT4	ENST00000358752.4	c.479G>A	p.Gly160Asp	missense_variant	1/1		NM_002033.4	ENSP00000351602	P1
PIWIL4	ENST00000543336.5	c.-121+623G>A		intron_variant, NMD_transcript_variant		2		ENSP00000444575

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1321518 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 647120

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.479G>A (p.G160D) alteration is located in exon 1 (coding exon 1) of the FUT4 gene. This alteration results from a G to A substitution at nucleotide position 479, causing the glycine (G) at amino acid position 160 to be replaced by an aspartic acid (D). 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	0.76
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.016	D
Polyphen		0.99	D
Vest4		0.41
MutPred		0.69		Loss of catalytic residue at A159 (P = 0.0479);
MVP		0.50
MPC		1.9
ClinPred		0.92	D
GERP RS		1.7
Varity_R		0.19
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-94277778;