rs148792489

chr4-507609-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001127178.3(PIGG):c.759+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000813 in 1,598,050 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00048 (9 hom.)
• Consequence: PIGG NM_001127178.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.405

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-507609-G-A is Benign according to our data. Variant chr4-507609-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00399 (607/152278) while in subpopulation AFR AF= 0.014 (580/41558). AF 95% confidence interval is 0.013. There are 3 homozygotes in gnomad4. There are 285 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGG	NM_001127178.3	c.759+16G>A		intron_variant		ENST00000453061.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGG	ENST00000453061.7	c.759+16G>A		intron_variant		1	NM_001127178.3	P4

Frequencies

GnomAD3 genomes AF: 0.00399 AC: 607 AN: 152160 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00119 AC: 281 AN: 235334 Hom.: 0 AF XY: 0.00104 AC XY: 132 AN XY: 127422

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.000461

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00138

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000287

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000479 AC: 693 AN: 1445772 Hom.: 9 Cov.: 28 AF XY: 0.000462 AC XY: 332 AN XY: 718096

Gnomad4 AFR exome AF: 0.0140

Gnomad4 AMR exome AF: 0.000622

Gnomad4 ASJ exome AF: 0.0000389

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00138

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000236

Gnomad4 OTH exome AF: 0.000922

GnomAD4 genome AF: 0.00399 AC: 607 AN: 152278 Hom.: 3 Cov.: 33 AF XY: 0.00383 AC XY: 285 AN XY: 74440

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00221 Hom.: 1

Bravo AF: 0.00470

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 08, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 08, 2021	- -

Intellectual disability, autosomal recessive 53 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.0
Dann	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs148792489; hg19: chr4-501398;