rs139014980

Variant names:

• chr20-32216732-G-C
• rs139014980
• NM_015352.2:c.542+11G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-32216732-G-C
• chr20-32216732-G-T
• chr20-32216732-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015352.2(POFUT1):​c.542+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,578,646 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (28 hom., cov: 32)
  • Exomes 𝑓: 0.019 (302 hom.)
• Consequence: POFUT1 NM_015352.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.22
• Publications: 1 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: G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 20-32216732-G-C is Benign according to our data. Variant chr20-32216732-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1170434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0142 (2156/152266) while in subpopulation NFE AF = 0.02 (1357/68018). AF 95% confidence interval is 0.0191. There are 28 homozygotes in GnomAd4. There are 1108 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 AD,AR gene

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.542+11G>C		intron	N/A	NP_056167.1	Q9H488-1
	POFUT1	NM_172236.2		c.542+11G>C		intron	N/A	NP_758436.1	Q9H488-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POFUT1	ENST00000375749.8	TSL:1 MANE Select	c.542+11G>C		intron	N/A	ENSP00000364902.3	Q9H488-1
	POFUT1	ENST00000375730.3	TSL:1	c.542+11G>C		intron	N/A	ENSP00000364882.3	Q9H488-2
	POFUT1	ENST00000921349.1		c.542+11G>C		intron	N/A	ENSP00000591408.1

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2156 AN: 152148 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.00439

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0409

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0199

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.0144 AC: 3612 AN: 251064 AF XY: 0.0144

Gnomad AFR exome AF: 0.00381

Gnomad AMR exome AF: 0.00571

Gnomad ASJ exome AF: 0.00110

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0413

Gnomad NFE exome AF: 0.0203

Gnomad OTH exome AF: 0.0150

GnomAD4 exome AF: 0.0188 AC: 26881 AN: 1426380 Hom.: 302 Cov.: 25 AF XY: 0.0183 AC XY: 13022 AN XY: 711792

African (AFR) AF: 0.00287 AC: 94 AN: 32736

American (AMR) AF: 0.00580 AC: 259 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 30 AN: 25912

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.00141 AC: 121 AN: 85540

European-Finnish (FIN) AF: 0.0409 AC: 2185 AN: 53396

Middle Eastern (MID) AF: 0.000874 AC: 5 AN: 5718

European-Non Finnish (NFE) AF: 0.0217 AC: 23377 AN: 1079718

Other (OTH) AF: 0.0137 AC: 810 AN: 59180

GnomAD4 genome AF: 0.0142 AC: 2156 AN: 152266 Hom.: 28 Cov.: 32 AF XY: 0.0149 AC XY: 1108 AN XY: 74450

African (AFR) AF: 0.00438 AC: 182 AN: 41536

American (AMR) AF: 0.00830 AC: 127 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.0409 AC: 434 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0200 AC: 1357 AN: 68018

Other (OTH) AF: 0.0109 AC: 23 AN: 2108

Alfa AF: 0.00692 Hom.: 2

Bravo AF: 0.0113

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Dowling-Degos disease 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.0
DANN	Benign	0.59
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs139014980; hg19: chr20-30804535;