1-172442356-A-G

Variant names:

• chr1-172442356-A-G
• rs2230471
• NM_153747.2:c.267T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002642.4(PIGC):​c.267T>C​(p.Gly89Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 1,612,940 control chromosomes in the GnomAD database, including 582,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (57064 hom., cov: 31)
  • Exomes 𝑓: 0.85 (525036 hom.)
• Consequence: PIGC NM_002642.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.136
• Publications: 18 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-172442356-A-G is Benign according to our data. Variant chr1-172442356-A-G is described in ClinVar as Benign. ClinVar VariationId is 595495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.136 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002642.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGC	NM_153747.2	MANE Select	c.267T>C	p.Gly89Gly	synonymous	Exon 2 of 2	NP_714969.1
	C1orf105	NM_139240.4	MANE Select	c.22-2717A>G		intron	N/A	NP_640333.3
	PIGC	NM_002642.4		c.267T>C	p.Gly89Gly	synonymous	Exon 2 of 2	NP_002633.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGC	ENST00000344529.5	TSL:1 MANE Select	c.267T>C	p.Gly89Gly	synonymous	Exon 2 of 2	ENSP00000356701.3
	C1orf105	ENST00000367727.9	TSL:1 MANE Select	c.22-2717A>G		intron	N/A	ENSP00000356700.4
	PIGC	ENST00000484368.1	TSL:1	n.96+1632T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131449 AN: 152020 Hom.: 57026 Cov.: 31

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.899

GnomAD2 exomes AF: 0.874 AC: 219695 AN: 251388 AF XY: 0.875

Gnomad AFR exome AF: 0.892

Gnomad AMR exome AF: 0.904

Gnomad ASJ exome AF: 0.924

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.774

Gnomad NFE exome AF: 0.839

Gnomad OTH exome AF: 0.882

GnomAD4 exome AF: 0.846 AC: 1236322 AN: 1460802 Hom.: 525036 Cov.: 63 AF XY: 0.850 AC XY: 617413 AN XY: 726730

African (AFR) AF: 0.896 AC: 29977 AN: 33454

American (AMR) AF: 0.905 AC: 40453 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 24140 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39681 AN: 39700

South Asian (SAS) AF: 0.935 AC: 80585 AN: 86208

European-Finnish (FIN) AF: 0.774 AC: 41359 AN: 53414

Middle Eastern (MID) AF: 0.950 AC: 4681 AN: 4928

European-Non Finnish (NFE) AF: 0.830 AC: 923241 AN: 1111938

Other (OTH) AF: 0.866 AC: 52205 AN: 60300

GnomAD4 genome AF: 0.865 AC: 131545 AN: 152138 Hom.: 57064 Cov.: 31 AF XY: 0.865 AC XY: 64332 AN XY: 74364

African (AFR) AF: 0.892 AC: 37018 AN: 41512

American (AMR) AF: 0.907 AC: 13870 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3234 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5173 AN: 5180

South Asian (SAS) AF: 0.944 AC: 4541 AN: 4812

European-Finnish (FIN) AF: 0.766 AC: 8101 AN: 10582

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56655 AN: 67974

Other (OTH) AF: 0.900 AC: 1898 AN: 2108

Alfa AF: 0.850 Hom.: 28314

Bravo AF: 0.877

Asia WGS AF: 0.964 AC: 3354 AN: 3478

EpiCase AF: 0.854

EpiControl AF: 0.859

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Glycosylphosphatidylinositol biosynthesis defect 16 (1)
-	-	1	not specified (1)
-	-	1	PIGC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.8
DANN	Benign	0.80
PhyloP100		0.14
Mutation Taster		=99/1	polymorphism (auto)

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: rs2230471; hg19: chr1-172411496; COSMIC: COSV51129928; COSMIC: COSV51129928;