20-32210173-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015352.2(POFUT1):ā€‹c.227A>Gā€‹(p.His76Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00012 ( 0 hom., cov: 32)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

POFUT1
NM_015352.2 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 8.59
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2122939).
BS2
High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
POFUT1NM_015352.2 linkuse as main transcriptc.227A>G p.His76Arg missense_variant 2/7 ENST00000375749.8 NP_056167.1
POFUT1NM_172236.2 linkuse as main transcriptc.227A>G p.His76Arg missense_variant 2/5 NP_758436.1
POFUT1XM_047440079.1 linkuse as main transcriptc.-79+2108A>G intron_variant XP_047296035.1
POFUT1XR_007067447.1 linkuse as main transcriptn.289A>G non_coding_transcript_exon_variant 2/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
POFUT1ENST00000375749.8 linkuse as main transcriptc.227A>G p.His76Arg missense_variant 2/71 NM_015352.2 ENSP00000364902 P1Q9H488-1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251482
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461848
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.000358
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.000410
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000222
Hom.:
0
Bravo
AF:
0.000159
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000576
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 27, 2021The c.227A>G (p.H76R) alteration is located in exon 2 (coding exon 2) of the POFUT1 gene. This alteration results from a A to G substitution at nucleotide position 227, causing the histidine (H) at amino acid position 76 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
22
DANN
Benign
0.73
DEOGEN2
Benign
0.10
T;.
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.19
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-1.7
N;N
REVEL
Benign
0.22
Sift
Benign
0.77
T;T
Sift4G
Benign
0.88
T;T
Polyphen
0.084
B;B
Vest4
0.80
MVP
0.43
MPC
0.32
ClinPred
0.14
T
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.46
gMVP
0.75

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.

Other links and lift over

dbSNP: rs142484235; hg19: chr20-30797976; API