rs75952679

Variant names:

• chr16-576227-G-C
• rs75952679
• NM_004204.5:c.915G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-576227-G-C
• chr16-576227-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004204.5(PIGQ):​c.915G>C​(p.Leu305Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00795 in 1,552,642 control chromosomes in the GnomAD database, including 530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (297 hom., cov: 34)
  • Exomes 𝑓: 0.0051 (233 hom.)
• Consequence: PIGQ NM_004204.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.81
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 77

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000282907 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 16-576227-G-C is Benign according to our data. Variant chr16-576227-G-C is described in ClinVar as Benign. ClinVar VariationId is 456055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.81 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004204.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGQ	NM_004204.5	MANE Select	c.915G>C	p.Leu305Leu	synonymous	Exon 4 of 11	NP_004195.2
	PIGQ	NM_148920.4		c.915G>C	p.Leu305Leu	synonymous	Exon 4 of 10	NP_683721.1	Q9BRB3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGQ	ENST00000321878.10	TSL:1 MANE Select	c.915G>C	p.Leu305Leu	synonymous	Exon 4 of 11	ENSP00000326674.6	Q9BRB3-2
	PIGQ	ENST00000026218.9	TSL:1	c.915G>C	p.Leu305Leu	synonymous	Exon 4 of 10	ENSP00000026218.5	Q9BRB3-1
	PIGQ	ENST00000470411.2	TSL:1	c.*178G>C		3_prime_UTR	Exon 3 of 3	ENSP00000439650.1	Q9BRB3-3

Frequencies

GnomAD3 genomes AF: 0.0339 AC: 5166 AN: 152226 Hom.: 294 Cov.: 34

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.0253

GnomAD2 exomes AF: 0.00913 AC: 1427 AN: 156338 AF XY: 0.00670

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.00809

Gnomad ASJ exome AF: 0.00307

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000331

Gnomad NFE exome AF: 0.00252

Gnomad OTH exome AF: 0.00613

GnomAD4 exome AF: 0.00511 AC: 7158 AN: 1400298 Hom.: 233 Cov.: 34 AF XY: 0.00465 AC XY: 3214 AN XY: 690960

African (AFR) AF: 0.113 AC: 3608 AN: 31822

American (AMR) AF: 0.00926 AC: 334 AN: 36062

Ashkenazi Jewish (ASJ) AF: 0.00246 AC: 62 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 36108

South Asian (SAS) AF: 0.000541 AC: 43 AN: 79424

European-Finnish (FIN) AF: 0.000188 AC: 9 AN: 47750

Middle Eastern (MID) AF: 0.0121 AC: 68 AN: 5606

European-Non Finnish (NFE) AF: 0.00225 AC: 2428 AN: 1080264

Other (OTH) AF: 0.0104 AC: 606 AN: 58086

GnomAD4 genome AF: 0.0341 AC: 5188 AN: 152344 Hom.: 297 Cov.: 34 AF XY: 0.0336 AC XY: 2506 AN XY: 74492

African (AFR) AF: 0.112 AC: 4667 AN: 41574

American (AMR) AF: 0.0167 AC: 256 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10632

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00284 AC: 193 AN: 68030

Other (OTH) AF: 0.0250 AC: 53 AN: 2116

Alfa AF: 0.0110 Hom.: 20

Bravo AF: 0.0380

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.2
DANN	Benign	0.30
PhyloP100		1.8
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs75952679; hg19: chr16-626227;