16-574108-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_004204.5(PIGQ):c.34G>A(p.Val12Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000521 in 1,609,696 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00031 (4 hom.)
• Consequence: PIGQ NM_004204.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.393

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006198168).
• BP6: Variant 16-574108-G-A is Benign according to our data. Variant chr16-574108-G-A is described in ClinVar as [Benign]. Clinvar id is 456045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00257 (391/152348) while in subpopulation AFR AF= 0.00871 (362/41566). AF 95% confidence interval is 0.00797. There are 1 homozygotes in gnomad4. There are 197 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGQ	NM_004204.5	c.34G>A	p.Val12Ile	missense_variant	2/11	ENST00000321878.10
PIGQ	NM_148920.4	c.34G>A	p.Val12Ile	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGQ	ENST00000321878.10	c.34G>A	p.Val12Ile	missense_variant	2/11	1	NM_004204.5	P1

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 391 AN: 152230 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.00873

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000826 AC: 203 AN: 245616 Hom.: 1 AF XY: 0.000584 AC XY: 78 AN XY: 133464

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.000988

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000362

Gnomad OTH exome AF: 0.000663

GnomAD4 exome AF: 0.000307 AC: 448 AN: 1457348 Hom.: 4 Cov.: 31 AF XY: 0.000269 AC XY: 195 AN XY: 724994

Gnomad4 AFR exome AF: 0.00858

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000495

Gnomad4 OTH exome AF: 0.000880

GnomAD4 genome AF: 0.00257 AC: 391 AN: 152348 Hom.: 1 Cov.: 34 AF XY: 0.00264 AC XY: 197 AN XY: 74500

Gnomad4 AFR AF: 0.00871

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000336 Hom.: 0

Bravo AF: 0.00273

ESP6500AA AF: 0.00886 AC: 39

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000948 AC: 115

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	3.3
Dann	Uncertain	0.98
DEOGEN2	Benign	0.022	T;.;.;.;.;T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.89	D;.;D;D;D;D;T
MetaRNN	Benign	0.0062	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.64	N;N;N;N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.095	T;T;T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T;T;T
Polyphen		0.10, 0.76, 0.51	.;B;B;.;.;P;P
Vest4		0.099, 0.098, 0.079, 0.094, 0.083
MVP		0.31
MPC		0.21
ClinPred		0.0035	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.030
gMVP		0.20

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: rs11864607; hg19: chr16-624108;