chr20-32208300-T-C

Position:

• chr20-32208300-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015352.2(POFUT1):​c.124+235T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,024 control chromosomes in the GnomAD database, including 8,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.27 (8598 hom., cov: 31)
• Consequence: POFUT1 NM_015352.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.712

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-32208300-T-C is Benign according to our data. Variant chr20-32208300-T-C is described in ClinVar as [Benign]. Clinvar id is 1244677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POFUT1	NM_015352.2	c.124+235T>C		intron_variant		ENST00000375749.8	NP_056167.1
POFUT1	NM_172236.2	c.124+235T>C		intron_variant			NP_758436.1
POFUT1	XM_047440079.1	c.-79+235T>C		intron_variant			XP_047296035.1
POFUT1	XR_007067447.1	n.186+235T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POFUT1	ENST00000375749.8	c.124+235T>C		intron_variant		1	NM_015352.2	ENSP00000364902	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41129 AN: 151906 Hom.: 8580 Cov.: 31

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.271 AC: 41203 AN: 152024 Hom.: 8598 Cov.: 31 AF XY: 0.265 AC XY: 19725 AN XY: 74312

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.0813

Gnomad4 FIN AF: 0.0993

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.242

Alfa AF: 0.143 Hom.: 509

Bravo AF: 0.302

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.38

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: rs6121388; hg19: chr20-30796103;