rs778970

Positions:

• chr19-5867166-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002034.2(FUT5):​c.560C>T​(p.Pro187Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,610,964 control chromosomes in the GnomAD database, including 170,867 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.42 (14191 hom., cov: 30)
  • Exomes 𝑓: 0.46 (156676 hom.)
• Consequence: FUT5 NM_002034.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.8676883E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUT5	NM_002034.2	c.560C>T	p.Pro187Leu	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.560C>T	p.Pro187Leu	missense_variant	2/2	1	NM_002034.2	ENSP00000466880	P1
FUT5	ENST00000252675.6	c.560C>T	p.Pro187Leu	missense_variant	1/1			ENSP00000252675	P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64248 AN: 151368 Hom.: 14179 Cov.: 30

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.411

GnomAD3 exomes AF: 0.473 AC: 115488 AN: 244406 Hom.: 28245 AF XY: 0.466 AC XY: 62297 AN XY: 133574

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.630

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.577

Gnomad SAS exome AF: 0.414

Gnomad FIN exome AF: 0.420

Gnomad NFE exome AF: 0.457

Gnomad OTH exome AF: 0.477

GnomAD4 exome AF: 0.462 AC: 674354 AN: 1459480 Hom.: 156676 Cov.: 84 AF XY: 0.460 AC XY: 333922 AN XY: 726054

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.622

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.622

Gnomad4 SAS exome AF: 0.419

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.455

GnomAD4 genome AF: 0.424 AC: 64293 AN: 151484 Hom.: 14191 Cov.: 30 AF XY: 0.427 AC XY: 31590 AN XY: 73950

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.412

Alfa AF: 0.440 Hom.: 6448

Bravo AF: 0.434

ExAC AF: 0.455 AC: 54709

EpiCase AF: 0.460

EpiControl AF: 0.454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Uncertain	0.99
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.77	T;.
MetaRNN	Benign	0.000029	T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.9	D;.
REVEL	Benign	0.077
Sift	Benign	0.31	T;.
Sift4G	Benign	0.092	T;T
Vest4		0.092
MPC		0.75
ClinPred		0.056	T
GERP RS		1.3
gMVP		0.34

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

LitVar

Other links and lift over

dbSNP: rs778970; hg19: chr19-5867177; COSMIC: COSV53134845; COSMIC: COSV53134845;