Genetic Variant POFUT1:p.Leu322Phe (chr20-32231047-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015352.2(POFUT1):c.964C>T(p.Leu322Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 1,614,008 control chromosomes in the GnomAD database, including 2,379 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 166 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2213 hom. )

Consequence

POFUT1
NM_015352.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

POFUT1 (HGNC:14988): (protein O-fucosyltransferase 1) This gene encodes a member of the glycosyltransferase O-Fuc family. This enzyme adds O-fucose through an O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cell surface and secreted proteins. O-fucose glycans are involved in ligand-induced receptor signaling. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

POFUT1 links:

LOC124904884 (HGNC:):

LOC124904884 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018129647).

BP6

Variant 20-32231047-C-T is Benign according to our data. Variant chr20-32231047-C-T is described in ClinVar as [Benign]. Clinvar id is 474296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POFUT1	NM_015352.2 link	c.964C>T	p.Leu322Phe	missense_variant	Exon 6 of 7	ENST00000375749.8	NP_056167.1	Q9H488-1
POFUT1	XM_047440079.1 link	c.640C>T	p.Leu214Phe	missense_variant	Exon 5 of 6		XP_047296035.1
LOC124904884	XR_007067560.1 link	n.-6G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POFUT1	ENST00000375749.8 link	c.964C>T	p.Leu322Phe	missense_variant	Exon 6 of 7	1	NM_015352.2	ENSP00000364902.3		Q9H488-1

Frequencies

GnomAD3 genomes

AF:

0.0399

AC:

6077

AN:

152190

Hom.:

166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.0629

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0466

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0560

Gnomad OTH

AF:

0.0535

GnomAD3 exomes

AF:

0.0408

AC:

10256

AN:

251454

Hom.:

286

AF XY:

0.0399

AC XY:

5420

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00978

Gnomad AMR exome

AF:

0.0465

Gnomad ASJ exome

AF:

0.0458

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00650

Gnomad FIN exome

AF:

0.0486

Gnomad NFE exome

AF:

0.0566

Gnomad OTH exome

AF:

0.0544

GnomAD4 exome

AF:

0.0512

AC:

74861

AN:

1461700

Hom.:

2213

Cov.:

AF XY:

0.0499

AC XY:

36282

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.00863

Gnomad4 AMR exome

AF:

0.0459

Gnomad4 ASJ exome

AF:

0.0464

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00691

Gnomad4 FIN exome

AF:

0.0486

Gnomad4 NFE exome

AF:

0.0586

Gnomad4 OTH exome

AF:

0.0474

GnomAD4 genome

AF:

0.0399

AC:

6075

AN:

152308

Hom.:

166

Cov.:

AF XY:

0.0400

AC XY:

2976

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0112

Gnomad4 AMR

AF:

0.0629

Gnomad4 ASJ

AF:

0.0415

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.0466

Gnomad4 NFE

AF:

0.0559

Gnomad4 OTH

AF:

0.0530

Alfa

AF:

0.0522

Hom.:

478

Bravo

AF:

0.0413

TwinsUK

AF:

0.0628

AC:

233

ALSPAC

AF:

0.0612

AC:

236

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.0563

AC:

484

ExAC

AF:

0.0391

AC:

4752

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dowling-Degos disease 2

Benign:1

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.72

REVEL

Benign

0.068

Sift

Benign

0.38

Sift4G

Benign

0.76

Polyphen

0.0030

Vest4

0.071

MPC

0.20

ClinPred

0.0052

GERP RS

3.3

Varity_R

0.067

gMVP

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over