20-32231047-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

Dowling-Degos disease 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Dowling-Degos disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

POFUT1 links:

LOC124904884 (HGNC:):

LOC124904884 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

GnomAD2 exomes

AF:

0.0408

AC:

10256

AN:

251454

AF XY:

0.0399

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 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

African (AFR)

AF:

0.00863

AC:

289

AN:

33480

American (AMR)

AF:

0.0459

AC:

2055

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0464

AC:

1212

AN:

26134

East Asian (EAS)

AF:

0.000202

AC:

AN:

39700

South Asian (SAS)

AF:

0.00691

AC:

596

AN:

86246

European-Finnish (FIN)

AF:

0.0486

AC:

2594

AN:

53414

Middle Eastern (MID)

AF:

0.0250

AC:

144

AN:

5768

European-Non Finnish (NFE)

AF:

0.0586

AC:

65103

AN:

1111840

Other (OTH)

AF:

0.0474

AC:

2860

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

3601

7201

10802

14402

18003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2398

4796

7194

9592

11990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0399

AC:

6075

AN:

152308

Hom.:

166

Cov.:

AF XY:

0.0400

AC XY:

2976

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0112

AC:

465

AN:

41562

American (AMR)

AF:

0.0629

AC:

962

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0415

AC:

144

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00331

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0466

AC:

495

AN:

10612

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0559

AC:

3805

AN:

68030

Other (OTH)

AF:

0.0530

AC:

112

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

287

574

862

1149

1436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0510

Hom.:

598

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

Jul 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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

PhyloP100

1.2

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

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over