NM_015352.2:c.75T>C

Variant names:

• chr20-32208016-T-C
• rs1923095
• NM_015352.2:c.75T>C

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.75T>C​(p.Pro25Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,580,522 control chromosomes in the GnomAD database, including 286,387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (37650 hom., cov: 33)
  • Exomes 𝑓: 0.58 (248737 hom.)
• Consequence: POFUT1 NM_015352.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.987
• Publications: 23 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 20-32208016-T-C is Benign according to our data. Variant chr20-32208016-T-C is described in ClinVar as Benign. ClinVar VariationId is 683580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.987 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POFUT1	NM_015352.2	MANE Select	c.75T>C	p.Pro25Pro	synonymous	Exon 1 of 7	NP_056167.1	Q9H488-1
	POFUT1	NM_172236.2		c.75T>C	p.Pro25Pro	synonymous	Exon 1 of 5	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.75T>C	p.Pro25Pro	synonymous	Exon 1 of 7	ENSP00000364902.3	Q9H488-1
	POFUT1	ENST00000375730.3	TSL:1	c.75T>C	p.Pro25Pro	synonymous	Exon 1 of 5	ENSP00000364882.3	Q9H488-2
	POFUT1	ENST00000921349.1		c.75T>C	p.Pro25Pro	synonymous	Exon 1 of 7	ENSP00000591408.1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104031 AN: 151976 Hom.: 37578 Cov.: 33

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.652

GnomAD2 exomes AF: 0.646 AC: 124513 AN: 192886 AF XY: 0.623

Gnomad AFR exome AF: 0.910

Gnomad AMR exome AF: 0.788

Gnomad ASJ exome AF: 0.508

Gnomad EAS exome AF: 0.997

Gnomad FIN exome AF: 0.620

Gnomad NFE exome AF: 0.562

Gnomad OTH exome AF: 0.597

GnomAD4 exome AF: 0.581 AC: 830173 AN: 1428426 Hom.: 248737 Cov.: 45 AF XY: 0.575 AC XY: 407885 AN XY: 708754

African (AFR) AF: 0.907 AC: 29804 AN: 32874

American (AMR) AF: 0.777 AC: 32362 AN: 41670

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 13091 AN: 25662

East Asian (EAS) AF: 0.998 AC: 38084 AN: 38172

South Asian (SAS) AF: 0.501 AC: 41521 AN: 82794

European-Finnish (FIN) AF: 0.626 AC: 26906 AN: 42962

Middle Eastern (MID) AF: 0.480 AC: 2731 AN: 5690

European-Non Finnish (NFE) AF: 0.555 AC: 610196 AN: 1099384

Other (OTH) AF: 0.599 AC: 35478 AN: 59218

GnomAD4 genome AF: 0.685 AC: 104163 AN: 152096 Hom.: 37650 Cov.: 33 AF XY: 0.687 AC XY: 51062 AN XY: 74352

African (AFR) AF: 0.900 AC: 37379 AN: 41530

American (AMR) AF: 0.693 AC: 10597 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1751 AN: 3472

East Asian (EAS) AF: 0.992 AC: 5110 AN: 5150

South Asian (SAS) AF: 0.525 AC: 2537 AN: 4828

European-Finnish (FIN) AF: 0.628 AC: 6635 AN: 10572

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38076 AN: 67938

Other (OTH) AF: 0.648 AC: 1368 AN: 2112

Alfa AF: 0.590 Hom.: 8734

Bravo AF: 0.707

Asia WGS AF: 0.773 AC: 2690 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Dowling-Degos disease 2 (2)
-	-	2	not provided (2)
-	-	1	POFUT1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.63
PhyloP100		-0.99
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1923095; hg19: chr20-30795819; COSMIC: COSV55788480; COSMIC: COSV55788480;