Variant 1-172442125-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_153747.2(PIGC):c.498T>C(p.Tyr166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000783 in 1,614,244 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 6 hom. )

Consequence

PIGC
NM_153747.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.207

Variant links:

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]

PIGC links:

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

C1orf105 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 1-172442125-A-G is Benign according to our data. Variant chr1-172442125-A-G is described in ClinVar as [Benign]. Clinvar id is 767727.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.207 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00431 (657/152360) while in subpopulation AFR AF= 0.0146 (608/41590). AF 95% confidence interval is 0.0137. There are 7 homozygotes in gnomad4. There are 321 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGC	NM_153747.2 linkuse as main transcript	c.498T>C	p.Tyr166=	synonymous_variant	2/2	ENST00000344529.5
C1orf105	NM_139240.4 linkuse as main transcript	c.22-2948A>G		intron_variant		ENST00000367727.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PIGC	ENST00000344529.5 linkuse as main transcript	c.498T>C	p.Tyr166=	synonymous_variant	2/2	1	NM_153747.2	P1
C1orf105	ENST00000367727.9 linkuse as main transcript	c.22-2948A>G		intron_variant		1	NM_139240.4	P1
PIGC	ENST00000484368.1 linkuse as main transcript	n.96+1863T>C		intron_variant, non_coding_transcript_variant		1
PIGC	ENST00000367728.1 linkuse as main transcript	c.498T>C	p.Tyr166=	synonymous_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.00428

AC:

651

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00115

AC:

289

AN:

251342

Hom.:

AF XY:

0.000928

AC XY:

126

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.0151

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000415

AC:

607

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000356

AC XY:

259

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00431

AC:

657

AN:

152360

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

321

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.00287

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00483

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 12, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.5

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over