chr4-523811-C-G

Variant names:

• chr4-523811-C-G
• rs61749092
• NM_001127178.3:c.1967C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001127178.3(PIGG):​c.1967C>G​(p.Ala656Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PIGG NM_001127178.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21955913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGG	NM_001127178.3	c.1967C>G	p.Ala656Gly	missense_variant	Exon 9 of 13	ENST00000453061.7	NP_001120650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGG	ENST00000453061.7	c.1967C>G	p.Ala656Gly	missense_variant	Exon 9 of 13	1	NM_001127178.3	ENSP00000415203.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247312 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134342

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000900

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460836 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726680

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	.;T;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	.;M;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.092	T;T;T;T
Sift4G	Benign	0.23	T;T;T;T
Polyphen		0.013	B;B;.;B
Vest4		0.42
MutPred		0.31		.;Loss of helix (P = 0.0376);.;.;
MVP		0.22
MPC		0.18
ClinPred		0.25	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.38

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: rs61749092; hg19: chr4-517600;