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GeneBe

rs11726338

chr4-516061-T-C

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

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.36 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 37 BG,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIGGNM_001127178.3 linkuse as main transcriptc.990T>C p.Ser330= synonymous_variant 6/13 ENST00000453061.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIGGENST00000453061.7 linkuse as main transcriptc.990T>C p.Ser330= synonymous_variant 6/131 NM_001127178.3 P4Q5H8A4-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0252
AC:
3840
AN:
152200
Hom.:
37
Cov.:
33
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.:
73
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.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0252
AC:
3841
AN:
152318
Hom.:
37
Cov.:
33
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.:
71
Bravo
AF:
0.0253
Asia WGS
AF:
0.00808
AC:
28
AN:
3478
EpiCase
AF:
0.0300
EpiControl
AF:
0.0302

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxMar 31, 2021- -
Intellectual disability, autosomal recessive 53 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 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.

Other links and lift over

dbSNP: rs11726338; hg19: chr4-509850; API