chr20-32208300-T-G

Position:

• chr20-32208300-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015352.2(POFUT1):​c.124+235T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 152,064 control chromosomes in the GnomAD database, including 28 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: 31)
• Consequence: POFUT1 NM_015352.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 20-32208300-T-G is Benign according to our data. Variant chr20-32208300-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1707140.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0142 (2152/152064) while in subpopulation NFE AF= 0.02 (1358/67970). AF 95% confidence interval is 0.0191. There are 28 homozygotes in gnomad4. There are 1106 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2152 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POFUT1	NM_015352.2	c.124+235T>G		intron_variant		ENST00000375749.8	NP_056167.1
POFUT1	NM_172236.2	c.124+235T>G		intron_variant			NP_758436.1
POFUT1	XM_047440079.1	c.-79+235T>G		intron_variant			XP_047296035.1
POFUT1	XR_007067447.1	n.186+235T>G		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>G		intron_variant		1	NM_015352.2	ENSP00000364902	P1

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2152 AN: 151946 Hom.: 28 Cov.: 31

Gnomad AFR AF: 0.00440

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.00812

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0408

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0200

Gnomad OTH AF: 0.0115

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

GnomAD4 genome AF: 0.0142 AC: 2152 AN: 152064 Hom.: 28 Cov.: 31 AF XY: 0.0149 AC XY: 1106 AN XY: 74336

Gnomad4 AFR AF: 0.00439

Gnomad4 AMR AF: 0.00811

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0408

Gnomad4 NFE AF: 0.0200

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00366 Hom.: 509

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 09, 2019

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.41

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;