chr20-32208016-T-C

Position:

• chr20-32208016-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015352.2(POFUT1):​c.75T>C​(p.Pro25=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POFUT1	NM_015352.2	c.75T>C	p.Pro25=	synonymous_variant	1/7	ENST00000375749.8	NP_056167.1
POFUT1	NM_172236.2	c.75T>C	p.Pro25=	synonymous_variant	1/5		NP_758436.1
POFUT1	XM_047440079.1	c.-128T>C		5_prime_UTR_variant	1/6		XP_047296035.1
POFUT1	XR_007067447.1	n.137T>C		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POFUT1	ENST00000375749.8	c.75T>C	p.Pro25=	synonymous_variant	1/7	1	NM_015352.2	ENSP00000364902	P1

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

GnomAD3 exomes AF: 0.646 AC: 124513 AN: 192886 Hom.: 42375 AF XY: 0.623 AC XY: 66083 AN XY: 106034

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 SAS exome AF: 0.497

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

Gnomad4 AFR exome AF: 0.907

Gnomad4 AMR exome AF: 0.777

Gnomad4 ASJ exome AF: 0.510

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.501

Gnomad4 FIN exome AF: 0.626

Gnomad4 NFE exome AF: 0.555

Gnomad4 OTH exome AF: 0.599

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

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.648

Alfa AF: 0.585 Hom.: 8434

Bravo AF: 0.707

Asia WGS AF: 0.773 AC: 2690 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dowling-Degos disease 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

POFUT1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

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