1-172442230-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_153747.2(PIGC):c.393T>C(p.Tyr131=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,613,998 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (3 hom.)
• Consequence: PIGC NM_153747.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.881

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-172442230-A-G is Benign according to our data. Variant chr1-172442230-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1299807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-172442230-A-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00108 (164/152366) while in subpopulation NFE AF= 0.00191 (130/68036). AF 95% confidence interval is 0.00164. There are 1 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGC	NM_153747.2	c.393T>C	p.Tyr131=	synonymous_variant	2/2	ENST00000344529.5
C1orf105	NM_139240.4	c.22-2843A>G		intron_variant		ENST00000367727.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGC	ENST00000344529.5	c.393T>C	p.Tyr131=	synonymous_variant	2/2	1	NM_153747.2	P1
C1orf105	ENST00000367727.9	c.22-2843A>G		intron_variant		1	NM_139240.4	P1
PIGC	ENST00000484368.1	n.96+1758T>C		intron_variant, non_coding_transcript_variant		1
PIGC	ENST00000367728.1	c.393T>C	p.Tyr131=	synonymous_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 163 AN: 152248 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00108 AC: 272 AN: 251032 Hom.: 0 AF XY: 0.00113 AC XY: 153 AN XY: 135742

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000784

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00197

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.00196 AC: 2863 AN: 1461632 Hom.: 3 Cov.: 40 AF XY: 0.00193 AC XY: 1402 AN XY: 727086

Gnomad4 AFR exome AF: 0.000358

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00109

Gnomad4 FIN exome AF: 0.000524

Gnomad4 NFE exome AF: 0.00238

Gnomad4 OTH exome AF: 0.00111

GnomAD4 genome AF: 0.00108 AC: 164 AN: 152366 Hom.: 1 Cov.: 32 AF XY: 0.00103 AC XY: 77 AN XY: 74502

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00191

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.00107

EpiCase AF: 0.00120

EpiControl AF: 0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Sep 19, 2023	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	PIGC: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.085
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs61747502; hg19: chr1-172411370;