rs1135945

Positions:

• chr4-522797-G-A
• chr4-522797-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000509768.1(PIGG):​c.*760G>A variant causes a 3 prime UTR 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 ENST00000509768.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGG	NM_001127178.3	c.1615-662G>A		intron_variant		ENST00000453061.7	NP_001120650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGG	ENST00000453061.7	c.1615-662G>A		intron_variant		1	NM_001127178.3	ENSP00000415203	P4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35975 AN: 152042 Hom.: 4506 Cov.: 33

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.: 18 Cov.: 0 AF XY: 0.166 AC XY: 82 AN XY: 494

Gnomad4 AMR exome AF: 0.0714

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0313

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.237 AC: 36039 AN: 152160 Hom.: 4527 Cov.: 33 AF XY: 0.234 AC XY: 17372 AN XY: 74390

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.236

Alfa AF: 0.201 Hom.: 3994

Bravo AF: 0.241

Asia WGS AF: 0.203 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs1135945; hg19: chr4-516586;