dbSNP rs6121388: POFUT1:c.124+235T>C (chr20-32208300-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.712

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
POFUT1	NM_015352.2 link	c.124+235T>C	intron_variant	Intron 1 of 6	ENST00000375749.8	NP_056167.1	Q9H488-1
POFUT1	NM_172236.2 link	c.124+235T>C	intron_variant	Intron 1 of 4		NP_758436.1	Q9H488-2
POFUT1	XM_047440079.1 link	c.-79+235T>C	intron_variant	Intron 1 of 5		XP_047296035.1
POFUT1	XR_007067447.1 link	n.186+235T>C	intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POFUT1	ENST00000375749.8 link	c.124+235T>C		intron_variant	Intron 1 of 6	1	NM_015352.2	ENSP00000364902.3		Q9H488-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41129

AN:

151906

Hom.:

8580

Cov.:

show subpopulations

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.:

AF XY:

0.265

AC XY:

19725

AN XY:

74312

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over