20-32228308-A-G

Variant names:

• chr20-32228308-A-G
• rs6579005
• NM_015352.2:c.588A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015352.2(POFUT1):​c.588A>G​(p.Pro196Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,613,994 control chromosomes in the GnomAD database, including 1,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (913 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (782 hom.)
• Consequence: POFUT1 NM_015352.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.82
• Publications: 4 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: 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

LOC124904884 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-32228308-A-G is Benign according to our data. Variant chr20-32228308-A-G is described in ClinVar as Benign. ClinVar VariationId is 474295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POFUT1	NM_015352.2	MANE Select	c.588A>G	p.Pro196Pro	synonymous	Exon 5 of 7	NP_056167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POFUT1	ENST00000375749.8	TSL:1 MANE Select	c.588A>G	p.Pro196Pro	synonymous	Exon 5 of 7	ENSP00000364902.3
	POFUT1	ENST00000465791.1	TSL:3	n.103A>G		non_coding_transcript_exon	Exon 2 of 3
	POFUT1	ENST00000486717.5	TSL:2	n.473A>G		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8810 AN: 152146 Hom.: 908 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0473

GnomAD2 exomes AF: 0.0147 AC: 3696 AN: 251024 AF XY: 0.0109

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.00899

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000423

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00587 AC: 8585 AN: 1461730 Hom.: 782 Cov.: 31 AF XY: 0.00500 AC XY: 3633 AN XY: 727176

African (AFR) AF: 0.208 AC: 6956 AN: 33466

American (AMR) AF: 0.00993 AC: 444 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.000574 AC: 15 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000371 AC: 32 AN: 86236

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00780 AC: 45 AN: 5768

European-Non Finnish (NFE) AF: 0.000281 AC: 312 AN: 1111912

Other (OTH) AF: 0.0129 AC: 780 AN: 60386

GnomAD4 genome AF: 0.0580 AC: 8833 AN: 152264 Hom.: 913 Cov.: 32 AF XY: 0.0557 AC XY: 4151 AN XY: 74458

African (AFR) AF: 0.201 AC: 8366 AN: 41526

American (AMR) AF: 0.0212 AC: 324 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68010

Other (OTH) AF: 0.0468 AC: 99 AN: 2116

Alfa AF: 0.0288 Hom.: 717

Bravo AF: 0.0657

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 04, 2021

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.72
DANN	Benign	0.52
PhyloP100		-2.8
Mutation Taster		=280/20	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6579005; hg19: chr20-30816111;