rs147306123

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_176787.5(PIGN):ā€‹c.1617T>Cā€‹(p.Tyr539=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,590,276 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0027 ( 1 hom., cov: 32)
Exomes š‘“: 0.0040 ( 14 hom. )

Consequence

PIGN
NM_176787.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.446
Variant links:
Genes affected
PIGN (HGNC:8967): (phosphatidylinositol glycan anchor biosynthesis class N) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is expressed in the endoplasmic reticulum and transfers phosphoethanolamine (EtNP) to the first mannose of the GPI anchor. Two alternatively spliced variants, which encode an identical isoform, have been reported. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 18-62107043-A-G is Benign according to our data. Variant chr18-62107043-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 472208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00265 (404/152306) while in subpopulation NFE AF= 0.00432 (294/68014). AF 95% confidence interval is 0.00392. There are 1 homozygotes in gnomad4. There are 183 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIGNNM_176787.5 linkuse as main transcriptc.1617T>C p.Tyr539= synonymous_variant 18/31 ENST00000640252.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIGNENST00000640252.2 linkuse as main transcriptc.1617T>C p.Tyr539= synonymous_variant 18/311 NM_176787.5 P1

Frequencies

GnomAD3 genomes
AF:
0.00265
AC:
404
AN:
152188
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000820
Gnomad AMI
AF:
0.0318
Gnomad AMR
AF:
0.000720
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00301
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00432
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00281
AC:
600
AN:
213260
Hom.:
1
AF XY:
0.00272
AC XY:
310
AN XY:
114174
show subpopulations
Gnomad AFR exome
AF:
0.000733
Gnomad AMR exome
AF:
0.000546
Gnomad ASJ exome
AF:
0.000109
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000155
Gnomad FIN exome
AF:
0.00267
Gnomad NFE exome
AF:
0.00540
Gnomad OTH exome
AF:
0.00149
GnomAD4 exome
AF:
0.00402
AC:
5777
AN:
1437970
Hom.:
14
Cov.:
29
AF XY:
0.00386
AC XY:
2750
AN XY:
712726
show subpopulations
Gnomad4 AFR exome
AF:
0.000700
Gnomad4 AMR exome
AF:
0.000525
Gnomad4 ASJ exome
AF:
0.000157
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000978
Gnomad4 FIN exome
AF:
0.00297
Gnomad4 NFE exome
AF:
0.00492
Gnomad4 OTH exome
AF:
0.00258
GnomAD4 genome
AF:
0.00265
AC:
404
AN:
152306
Hom.:
1
Cov.:
32
AF XY:
0.00246
AC XY:
183
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.000818
Gnomad4 AMR
AF:
0.000719
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00301
Gnomad4 NFE
AF:
0.00432
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.00356
Hom.:
1
Bravo
AF:
0.00245
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2024PIGN: BP4, BP7 -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsMar 14, 2018- -
Likely benign, criteria provided, single submitterclinical testingGeneDxOct 13, 2020- -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 24, 2016This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Multiple congenital anomalies-hypotonia-seizures syndrome 1 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
PIGN-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 28, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
3.2
DANN
Benign
0.35

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.

Other links and lift over

dbSNP: rs147306123; hg19: chr18-59774276; COSMIC: COSV100716362; COSMIC: COSV100716362; API