1-172441825-TGG-GCT

Variant names:

• chr1-172441825-TGG-GCT
• NM_153747.2:c.796_798delCCAinsAGC
• PIGC p.Pro266Ser

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM1 PP3

The NM_153747.2(PIGC):​c.796_798delCCAinsAGC​(p.Pro266Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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 Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIGC NM_153747.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.19
• Publications: 0 publications found

Genes affected

PIGC (HGNC:8960): (phosphatidylinositol glycan anchor biosynthesis class C) This gene encodes an endoplasmic reticulum associated protein that is involved in glycosylphosphatidylinositol (GPI) lipid anchor biosynthesis. The GPI lipid anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. The encoded protein is one subunit of the GPI N-acetylglucosaminyl (GlcNAc) transferase that transfers GlcNAc to phosphatidylinositol (PI) on the cytoplasmic side of the endoplasmic reticulum. Two alternatively spliced transcripts that encode the same protein have been found for this gene. A pseudogene on chromosome 11 has also been characterized. [provided by RefSeq, Jul 2008]

C1orf105 (HGNC:29591): (chromosome 1 open reading frame 105)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM1: In a chain Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (size 296) in uniprot entity PIGC_HUMAN there are 5 pathogenic changes around while only 2 benign (71%) in NM_153747.2
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153747.2. 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
	PIGC	NM_153747.2	MANE Select	c.796_798delCCAinsAGC	p.Pro266Ser	missense	N/A	NP_714969.1	Q92535
	C1orf105	NM_139240.4	MANE Select	c.22-3248_22-3246delTGGinsGCT		intron	N/A	NP_640333.3
	PIGC	NM_002642.4		c.796_798delCCAinsAGC	p.Pro266Ser	missense	N/A	NP_002633.1	Q92535

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGC	ENST00000344529.5	TSL:1 MANE Select	c.796_798delCCAinsAGC	p.Pro266Ser	missense	N/A	ENSP00000356701.3	Q92535
	C1orf105	ENST00000367727.9	TSL:1 MANE Select	c.22-3248_22-3246delTGGinsGCT		intron	N/A	ENSP00000356700.4	O95561
	PIGC	ENST00000484368.1	TSL:1	n.96+2161_96+2163delCCAinsAGC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.2

Splicing

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: chr1-172410965;