Variant 4-516061-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001127178.3(PIGG):c.990T>C(p.Ser330=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,613,996 control chromosomes in the GnomAD database, including 580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 37 hom., cov: 33)

Exomes 𝑓: 0.026 ( 543 hom. )

Consequence

PIGG
NM_001127178.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.36

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 4-516061-T-C is Benign according to our data. Variant chr4-516061-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 476358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.36 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0252 (3841/152318) while in subpopulation NFE AF= 0.0283 (1927/68016). AF 95% confidence interval is 0.0273. There are 37 homozygotes in gnomad4. There are 1738 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGG	NM_001127178.3 linkuse as main transcript	c.990T>C	p.Ser330=	synonymous_variant	6/13	ENST00000453061.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGG	ENST00000453061.7 linkuse as main transcript	c.990T>C	p.Ser330=	synonymous_variant	6/13	1	NM_001127178.3	P4	Q5H8A4-1

Frequencies

GnomAD3 genomes

AF:

0.0252

AC:

3840

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0276

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0210

AC:

5276

AN:

251494

Hom.:

AF XY:

0.0211

AC XY:

2862

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0279

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.0302

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0138

Gnomad FIN exome

AF:

0.0140

Gnomad NFE exome

AF:

0.0287

Gnomad OTH exome

AF:

0.0221

GnomAD4 exome

AF:

0.0259

AC:

37915

AN:

1461678

Hom.:

543

Cov.:

AF XY:

0.0257

AC XY:

18668

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.0128

Gnomad4 ASJ exome

AF:

0.0311

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0148

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0287

Gnomad4 OTH exome

AF:

0.0243

GnomAD4 genome

AF:

0.0252

AC:

3841

AN:

152318

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1738

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0275

Gnomad4 AMR

AF:

0.0199

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0176

Gnomad4 FIN

AF:

0.0127

Gnomad4 NFE

AF:

0.0283

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0279

Hom.:

Bravo

AF:

0.0253

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0300

EpiControl

AF:

0.0302

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Intellectual disability, autosomal recessive 53

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.055

DANN

Benign

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over