rs6579005

chr20-32228308-A-G

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.588A>G(p.Pro196=) 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:2
• Conservation: PhyloP100: -2.82

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]

LOC124904884 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POFUT1	NM_015352.2	c.588A>G	p.Pro196=	synonymous_variant	5/7	ENST00000375749.8
LOC124904884	XR_007067560.1	n.940T>C		non_coding_transcript_exon_variant	2/2
POFUT1	XM_047440079.1	c.264A>G	p.Pro88=	synonymous_variant	4/6
POFUT1	XR_007067447.1	n.851A>G		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POFUT1	ENST00000375749.8	c.588A>G	p.Pro196=	synonymous_variant	5/7	1	NM_015352.2	P1

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

GnomAD3 exomes AF: 0.0147 AC: 3696 AN: 251024 Hom.: 332 AF XY: 0.0109 AC XY: 1474 AN XY: 135676

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 SAS exome AF: 0.000392

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

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.00993

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000371

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000281

Gnomad4 OTH exome AF: 0.0129

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

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.0212

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.0468

Alfa AF: 0.0154 Hom.: 254

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dowling-Degos disease 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.72
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs6579005; hg19: chr20-30816111;