1-172441811-C-A

Variant names:

• chr1-172441811-C-A
• NM_153747.2:c.812G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_153747.2(PIGC):​c.812G>T​(p.Arg271Leu) 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 1,459,578 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R271H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PIGC NM_153747.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a chain Phosphatidylinositol N-acetylglucosaminyltransferase subunit C (size 296) in uniprot entity PIGC_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_153747.2
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGC	NM_153747.2	c.812G>T	p.Arg271Leu	missense_variant	Exon 2 of 2	ENST00000344529.5	NP_714969.1
C1orf105	NM_139240.4	c.22-3262C>A		intron_variant	Intron 1 of 6	ENST00000367727.9	NP_640333.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGC	ENST00000344529.5	c.812G>T	p.Arg271Leu	missense_variant	Exon 2 of 2	1	NM_153747.2	ENSP00000356701.3
C1orf105	ENST00000367727.9	c.22-3262C>A		intron_variant	Intron 1 of 6	1	NM_139240.4	ENSP00000356700.4
PIGC	ENST00000484368.1	n.96+2177G>T		intron_variant	Intron 1 of 4	1
PIGC	ENST00000367728.1	c.812G>T	p.Arg271Leu	missense_variant	Exon 1 of 1	6		ENSP00000356702.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459578 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725846

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.090
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.25	B;B
Vest4		0.66
MutPred		0.56		Loss of ubiquitination at K276 (P = 0.0672);Loss of ubiquitination at K276 (P = 0.0672);
MVP		0.63
MPC		0.36
ClinPred		0.95	D
GERP RS		2.1
Varity_R		0.25
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-172410951;