19-5866668-G-T

Position:

• chr19-5866668-G-T

Variant summary

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

The NM_002034.2(FUT5):​c.1058C>A​(p.Ala353Asp) 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: 29)
• Consequence: FUT5 NM_002034.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51

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]

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
FUT5	NM_002034.2	c.1058C>A	p.Ala353Asp	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	c.1058C>A	p.Ala353Asp	missense_variant	2/2	1	NM_002034.2	ENSP00000466880	P1
FUT5	ENST00000252675.6	c.1058C>A	p.Ala353Asp	missense_variant	1/1			ENSP00000252675	P1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 89

GnomAD4 genome Cov.: 29

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

May 01, 2022

The c.1058C>A (p.A353D) alteration is located in exon 2 (coding exon 1) of the FUT5 gene. This alteration results from a C to A substitution at nucleotide position 1058, causing the alanine (A) at amino acid position 353 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	0.87
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Uncertain	0.20
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.76	T;.
M_CAP	Benign	0.0043	T
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	0.93	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.0	D;.
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0050	D;D
Vest4		0.52
MutPred		0.77		Loss of MoRF binding (P = 0.0198);Loss of MoRF binding (P = 0.0198);
MVP		0.62
MPC		1.8
ClinPred		1.0	D
GERP RS		-0.29
gMVP		0.72

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: chr19-5866679;