PIGG p.Ser237Arg

Variant names:

• chr4-507543-A-C
• NM_001127178.3:c.709A>C
• PIGG p.Ser237Arg

Your query was ambiguous. Multiple possible variants found:

• chr4-507543-A-C
• chr4-507545-C-A
• chr4-507545-C-G
• chr4-507543-AGC-CGT
• chr4-507543-AGC-CGA
• chr4-507543-AGC-CGG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001127178.3(PIGG):​c.709A>C​(p.Ser237Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S237N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIGG NM_001127178.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 0 publications found

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]

PIGG Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 53

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06729606).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127178.3. 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
	PIGG	NM_001127178.3	MANE Select	c.709A>C	p.Ser237Arg	missense	Exon 4 of 13	NP_001120650.1	Q5H8A4-1
	PIGG	NM_017733.5		c.709A>C	p.Ser237Arg	missense	Exon 4 of 13	NP_060203.3
	PIGG	NM_001289051.2		c.442A>C	p.Ser148Arg	missense	Exon 4 of 13	NP_001275980.1	E7EWV1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGG	ENST00000453061.7	TSL:1 MANE Select	c.709A>C	p.Ser237Arg	missense	Exon 4 of 13	ENSP00000415203.2	Q5H8A4-1
	PIGG	ENST00000509768.1	TSL:1	c.442A>C	p.Ser148Arg	missense	Exon 4 of 8	ENSP00000421550.1	D6RFE8
	PIGG	ENST00000383028.8	TSL:1	c.361-1286A>C		intron	N/A	ENSP00000372494.4	Q5H8A4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.30
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N
PhyloP100		-0.080
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.089
Sift	Benign	0.87	T
Sift4G	Benign	0.74	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.061
gMVP		0.66
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-501332;