Genetic Variant PIGG:n.*877G>A (chr4-522797-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000506402.5(PIGG):n.*877G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 153,106 control chromosomes in the GnomAD database, including 4,545 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4527 hom., cov: 33)

Exomes 𝑓: 0.17 ( 18 hom. )

Consequence

PIGG
ENST00000506402.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.687

Publications

7 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

PIGG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000506402.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PIGG	NM_001127178.3	MANE Select	c.1615-662G>A	intron	N/A	NP_001120650.1
PIGG	NM_001345989.2		c.*584G>A	3_prime_UTR	Exon 9 of 9	NP_001332918.1
PIGG	NM_001289053.2		c.*760G>A	3_prime_UTR	Exon 8 of 8	NP_001275982.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PIGG	ENST00000506402.5	TSL:1	n.*877G>A	non_coding_transcript_exon	Exon 9 of 9	ENSP00000424619.1
PIGG	ENST00000509768.1	TSL:1	c.*760G>A	3_prime_UTR	Exon 8 of 8	ENSP00000421550.1
PIGG	ENST00000506402.5	TSL:1	n.*877G>A	3_prime_UTR	Exon 9 of 9	ENSP00000424619.1

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

35975

AN:

152042

Hom.:

4506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.223

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.178

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.236

GnomAD4 exome

AF:

0.171

AC:

162

AN:

946

Hom.:

Cov.:

AF XY:

0.166

AC XY:

AN XY:

494

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.0714

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0313

AC:

AN:

European-Finnish (FIN)

AF:

0.429

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.182

AC:

140

AN:

768

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

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:

0.237

AC:

36039

AN:

152160

Hom.:

4527

Cov.:

AF XY:

0.234

AC XY:

17372

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.331

AC:

13750

AN:

41494

American (AMR)

AF:

0.174

AC:

2654

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

865

AN:

3468

East Asian (EAS)

AF:

0.222

AC:

1148

AN:

5164

South Asian (SAS)

AF:

0.176

AC:

849

AN:

4820

European-Finnish (FIN)

AF:

0.202

AC:

2144

AN:

10596

Middle Eastern (MID)

AF:

0.182

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.204

AC:

13864

AN:

68008

Other (OTH)

AF:

0.236

AC:

498

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1408

2817

4225

5634

7042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.207

Hom.:

5870

Bravo

AF:

0.241

Asia WGS

AF:

0.203

AC:

703

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.4

(source)

DANN

Benign

0.52

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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