rs1647325450

Variant names:

• chr1-172441742-C-A
• rs1647325450
• NM_153747.2:c.881G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-172441742-C-A
• chr1-172441742-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM1 BP4

The NM_153747.2(PIGC):​c.881G>T​(p.Arg294Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000388 in 1,547,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: PIGC NM_153747.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• 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 1 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 1 benign (83%) in NM_153747.2
• BP4: Computational evidence support a benign effect (MetaRNN=0.3989043).

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.881G>T	p.Arg294Met	missense	Exon 2 of 2	NP_714969.1	Q92535
	C1orf105	NM_139240.4	MANE Select	c.22-3331C>A		intron	N/A	NP_640333.3
	PIGC	NM_002642.4		c.881G>T	p.Arg294Met	missense	Exon 2 of 2	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.881G>T	p.Arg294Met	missense	Exon 2 of 2	ENSP00000356701.3	Q92535
	C1orf105	ENST00000367727.9	TSL:1 MANE Select	c.22-3331C>A		intron	N/A	ENSP00000356700.4	O95561
	PIGC	ENST00000484368.1	TSL:1	n.96+2246G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00000358 AC: 5 AN: 1395516 Hom.: 0 Cov.: 30 AF XY: 0.00000727 AC XY: 5 AN XY: 687508

African (AFR) AF: 0.00 AC: 0 AN: 31270

American (AMR) AF: 0.00 AC: 0 AN: 33762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21732

East Asian (EAS) AF: 0.00 AC: 0 AN: 39144

South Asian (SAS) AF: 0.00 AC: 0 AN: 74060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51022

Middle Eastern (MID) AF: 0.000751 AC: 4 AN: 5324

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1081766

Other (OTH) AF: 0.00 AC: 0 AN: 57436

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74336

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Glycosylphosphatidylinositol biosynthesis defect 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.052	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.52
MutPred		0.35		Loss of solvent accessibility (P = 0.0364)
MVP		0.67
MPC		0.53
ClinPred		0.80	D
GERP RS		5.4
Varity_R		0.33
gMVP		0.55
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs1647325450; hg19: chr1-172410882;