Genetic Variant PIGG:p.Pro744Leu (chr4-527200-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001127178.3(PIGG):c.2231C>T(p.Pro744Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000804 in 1,603,668 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P744P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

PIGG
NM_001127178.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.93

Publications

0 publications found

Variant links:

Genes affected

PIGG (HGNC:25985): (phosphatidylinositol glycan anchor biosynthesis class G (EMM blood group)) This gene encodes an enzyme involved in glycosylphosphatidylinositol-anchor biosynthesis. The encoded protein, which is localized to the endoplasmic reticulum, is involved in transferring ethanoloamine phosphate to mannose 2 of glycosylphosphatidylinositol species H7 to form species H8. Allelic variants of this gene have been associated with intellectual disability, hypotonia, and early-onset seizures. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

PIGG Gene-Disease associations (from GenCC):

intellectual disability, autosomal recessive 53
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

PIGG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127178.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIGG	NM_001127178.3	MANE Select	c.2231C>T	p.Pro744Leu	missense	Exon 10 of 13	NP_001120650.1	Q5H8A4-1
PIGG	NM_017733.5		c.2207C>T	p.Pro736Leu	missense	Exon 10 of 13	NP_060203.3
PIGG	NM_001289051.2		c.1964C>T	p.Pro655Leu	missense	Exon 10 of 13	NP_001275980.1	E7EWV1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIGG	ENST00000453061.7	TSL:1 MANE Select	c.2231C>T	p.Pro744Leu	missense	Exon 10 of 13	ENSP00000415203.2	Q5H8A4-1
PIGG	ENST00000383028.8	TSL:1	c.1832C>T	p.Pro611Leu	missense	Exon 8 of 11	ENSP00000372494.4	Q5H8A4-3
PIGG	ENST00000510235.1	TSL:3	c.-248C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000422410.1	D6RC16

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000133

AC:

AN:

240428

AF XY:

0.000169

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000475

Gnomad NFE exome

AF:

0.00000921

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.0000792

AC:

115

AN:

1451366

Hom.:

Cov.:

AF XY:

0.0000999

AC XY:

AN XY:

720972

show subpopulations

African (AFR)

AF:

0.000544

AC:

AN:

33076

American (AMR)

AF:

0.00

AC:

AN:

43090

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25572

East Asian (EAS)

AF:

0.00

AC:

AN:

39508

South Asian (SAS)

AF:

0.000788

AC:

AN:

84980

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5294

European-Non Finnish (NFE)

AF:

0.0000154

AC:

AN:

1106798

Other (OTH)

AF:

0.000200

AC:

AN:

59886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.0000919

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41564

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.00

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Intellectual disability, autosomal recessive 53 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

6.9

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.2

REVEL

Uncertain

0.42

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.90

MVP

0.52

MPC

0.70

ClinPred

0.57

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.69

Mutation Taster

=53/47

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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