rs746870615

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_032634.4(PIGO):c.1132C>T(p.Leu378Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000103 in 1,605,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

PIGO
NM_032634.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:7

Conservation

PhyloP100: 6.25

Publications

2 publications found

Variant links:

Genes affected

PIGO (HGNC:23215): (phosphatidylinositol glycan anchor biosynthesis class O) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid which contains three mannose molecules in its core backbone. The GPI-anchor is found on many blood cells and serves to anchor proteins to the cell surface. This protein is involved in the transfer of ethanolaminephosphate (EtNP) to the third mannose in GPI. At least three alternatively spliced transcripts encoding two distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

PIGO Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hyperphosphatasia with intellectual disability syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina
hyperphosphatasia-intellectual disability syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PIGO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000963 (140/1453184) while in subpopulation MID AF = 0.00515 (28/5436). AF 95% confidence interval is 0.00366. There are 0 homozygotes in GnomAdExome4. There are 77 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032634.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIGO	NM_032634.4	MANE Select	c.1132C>T	p.Leu378Phe	missense	Exon 7 of 11	NP_116023.2
PIGO	NM_001201484.2		c.1132C>T	p.Leu378Phe	missense	Exon 8 of 13	NP_001188413.1	Q8TEQ8-2
PIGO	NM_152850.4		c.1132C>T	p.Leu378Phe	missense	Exon 7 of 12	NP_690577.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIGO	ENST00000378617.4	TSL:1 MANE Select	c.1132C>T	p.Leu378Phe	missense	Exon 7 of 11	ENSP00000367880.3	Q8TEQ8-1
PIGO	ENST00000298004.9	TSL:1	c.1132C>T	p.Leu378Phe	missense	Exon 8 of 13	ENSP00000298004.5	Q8TEQ8-2
PIGO	ENST00000907113.1		c.1132C>T	p.Leu378Phe	missense	Exon 7 of 11	ENSP00000577172.1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000144

AC:

AN:

236606

AF XY:

0.000109

show subpopulations

Gnomad AFR exome

AF:

0.0000654

Gnomad AMR exome

AF:

0.000466

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000151

Gnomad OTH exome

AF:

0.000354

GnomAD4 exome

AF:

0.0000963

AC:

140

AN:

1453184

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

723048

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

32738

American (AMR)

AF:

0.000424

AC:

AN:

42472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25634

East Asian (EAS)

AF:

0.00

AC:

AN:

39646

South Asian (SAS)

AF:

0.0000352

AC:

AN:

85160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52952

Middle Eastern (MID)

AF:

0.00515

AC:

AN:

5436

European-Non Finnish (NFE)

AF:

0.0000649

AC:

AN:

1109272

Other (OTH)

AF:

0.000251

AC:

AN:

59874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000164

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41458

American (AMR)

AF:

0.000327

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00316

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68046

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000657

Hom.:

Bravo

AF:

0.000147

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Hyperphosphatasia with intellectual disability syndrome 2 (2)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.4

PhyloP100

6.3

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.24

Sift

Uncertain

0.0070

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.73

MVP

0.78

MPC

0.68

ClinPred

0.12

GERP RS

5.5

Varity_R

0.21

gMVP

0.62

Mutation Taster

=45/55

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over