PIGG p.Leu463Leu

Variant names:

• chr4-521713-G-G
• ENST00000453061.7:c.

Your query was ambiguous. Multiple possible variants found:

• chr4-521714--
• chr4-521714-C-T
• chr4-521716-G-T
• chr4-521716-G-C
• chr4-521716-G-A
• chr4-521714-CTG-TTA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000453061.7(PIGG):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIGG ENST00000453061.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000453061.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGG	ENST00000453061.7	TSL:1 MANE Select	c.		intron	N/A	ENSP00000415203.2	Q5H8A4-1
	PIGG	ENST00000383028.8	TSL:1	c.		intron	N/A	ENSP00000372494.4	Q5H8A4-3
	PIGG	ENST00000310340.9	TSL:2	c.		intron	N/A	ENSP00000311750.5	Q5H8A4-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-515502;