Genetic Variant NM_004204.5:c.1461C>G (chr16-580902-C-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004204.5(PIGQ):c.1461C>G(p.Leu487Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,602,088 control chromosomes in the GnomAD database, including 28,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L487L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.17 ( 2298 hom., cov: 33)

Exomes 𝑓: 0.19 ( 26562 hom. )

Consequence

PIGQ
NM_004204.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.32

Variant links:

Genes affected

PIGQ (HGNC:14135): (phosphatidylinositol glycan anchor biosynthesis class Q) This gene is involved in the first step in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This gene encodes a N-acetylglucosaminyl transferase component that is part of the complex that catalyzes transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

PIGQ 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=-0.48).

BP6

Variant 16-580902-C-G is Benign according to our data. Variant chr16-580902-C-G is described in ClinVar as [Benign]. Clinvar id is 1164855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.32 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGQ	NM_004204.5 link	c.1461C>G	p.Leu487Leu	synonymous_variant	Exon 9 of 11	ENST00000321878.10	NP_004195.2	Q9BRB3-2B2RAU6
PIGQ	NM_148920.4 link	c.1461C>G	p.Leu487Leu	synonymous_variant	Exon 9 of 10		NP_683721.1	Q9BRB3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGQ	ENST00000321878.10 link	c.1461C>G	p.Leu487Leu	synonymous_variant	Exon 9 of 11	1	NM_004204.5	ENSP00000326674.6		Q9BRB3-2

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25175

AN:

152068

Hom.:

2295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.0990

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.0272

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.127

GnomAD3 exomes

AF:

0.160

AC:

40039

AN:

249526

Hom.:

3811

AF XY:

0.169

AC XY:

22841

AN XY:

135100

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.0605

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.0232

Gnomad SAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.152

GnomAD4 exome

AF:

0.185

AC:

268764

AN:

1449902

Hom.:

26562

Cov.:

AF XY:

0.188

AC XY:

135640

AN XY:

721910

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.0644

Gnomad4 ASJ exome

AF:

0.159

Gnomad4 EAS exome

AF:

0.0449

Gnomad4 SAS exome

AF:

0.257

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.174

GnomAD4 genome

AF:

0.166

AC:

25193

AN:

152186

Hom.:

2298

Cov.:

AF XY:

0.164

AC XY:

12214

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.0989

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.0273

Gnomad4 SAS

AF:

0.257

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.106

Hom.:

233

Bravo

AF:

0.155

Asia WGS

AF:

0.165

AC:

576

AN:

3478

EpiCase

AF:

0.176

EpiControl

AF:

0.171

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Epilepsy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy, 77

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

1.3

DANN

Benign

0.50

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