chr16-574503-G-A

Position:

• chr16-574503-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2 BP4_Strong BP6_Very_Strong BP7 BS1

The NM_004204.5(PIGQ):​c.429G>A​(p.Leu143Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,607,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: PIGQ NM_004204.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.27

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]

ENSG00000282907 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-574503-G-A is Benign according to our data. Variant chr16-574503-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 526285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.27 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000201 (293/1455314) while in subpopulation MID AF= 0.00264 (15/5688). AF 95% confidence interval is 0.00162. There are 0 homozygotes in gnomad4_exome. There are 152 alleles in male gnomad4_exome subpopulation. Median coverage is 40. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGQ	NM_004204.5	c.429G>A	p.Leu143Leu	synonymous_variant	2/11	ENST00000321878.10	NP_004195.2
PIGQ	NM_148920.4	c.429G>A	p.Leu143Leu	synonymous_variant	2/10		NP_683721.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGQ	ENST00000321878.10	c.429G>A	p.Leu143Leu	synonymous_variant	2/11	1	NM_004204.5	ENSP00000326674.6

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152188 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000258 AC: 60 AN: 232620 Hom.: 0 AF XY: 0.000243 AC XY: 31 AN XY: 127500

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000179

Gnomad ASJ exome AF: 0.000727

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000681

Gnomad FIN exome AF: 0.0000510

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.000876

GnomAD4 exome AF: 0.000201 AC: 293 AN: 1455314 Hom.: 0 Cov.: 40 AF XY: 0.000210 AC XY: 152 AN XY: 723536

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000158

Gnomad4 ASJ exome AF: 0.000808

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000469

Gnomad4 FIN exome AF: 0.0000195

Gnomad4 NFE exome AF: 0.000206

Gnomad4 OTH exome AF: 0.000266

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152306 Hom.: 0 Cov.: 34 AF XY: 0.000175 AC XY: 13 AN XY: 74472

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000282 Hom.: 0

Bravo AF: 0.000215

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	PIGQ: BP4, BP7 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PIGQ-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Epilepsy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0070
DANN	Benign	0.52

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: rs33997204; hg19: chr16-624503;