POFUT1 p.Arg385Arg

Variant names:

• chr20-32234646-G-G
• NM_015352.2:c.

Your query was ambiguous. Multiple possible variants found:

• chr20-32234647--
• chr20-32234649-G-T
• chr20-32234649-G-C
• chr20-32234649-G-A
• chr20-32234647-C-A
• chr20-32234647-CGG-AGA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015352.2(POFUT1):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: POFUT1 NM_015352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 0 publications found

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: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Dowling-Degos disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015352.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POFUT1	NM_015352.2	MANE Select	c.		intron	N/A	NP_056167.1	Q9H488-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POFUT1	ENST00000486717.5	TSL:2	n.		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-30822449;