rs2290344

Variant names:

• chr15-55327598-T-C
• rs2290344
• NM_004855.5:c.485T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004855.5(PIGB):​c.485T>C​(p.Met162Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,610,112 control chromosomes in the GnomAD database, including 19,526 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M162V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.12 (1910 hom., cov: 32)
  • Exomes 𝑓: 0.13 (17616 hom.)
• Consequence: PIGB NM_004855.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.83
• Publications: 27 publications found

Genes affected

PIGB (HGNC:8959): (phosphatidylinositol glycan anchor biosynthesis class B) This gene encodes a transmembrane protein that is located in the endoplasmic reticulum and is involved in GPI-anchor biosynthesis. The glycosylphosphatidylinositol (GPI) anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This gene is thought to encode a member of a family of dolichol-phosphate-mannose (Dol-P-Man) dependent mannosyltransferases. [provided by RefSeq, Jul 2008]

PIGB Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 80

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.1926584E-4).
• BP6: Variant 15-55327598-T-C is Benign according to our data. Variant chr15-55327598-T-C is described in ClinVar as Benign. ClinVar VariationId is 1585299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGB	NM_004855.5	c.485T>C	p.Met162Thr	missense_variant	Exon 4 of 12	ENST00000164305.10	NP_004846.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGB	ENST00000164305.10	c.485T>C	p.Met162Thr	missense_variant	Exon 4 of 12	1	NM_004855.5	ENSP00000164305.5
PIGB	ENST00000566999.5	c.458T>C	p.Met153Thr	missense_variant	Exon 4 of 6	3		ENSP00000456531.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18164 AN: 152106 Hom.: 1911 Cov.: 32

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.176 AC: 43378 AN: 246248 AF XY: 0.172

Gnomad AFR exome AF: 0.0315

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.121

Gnomad EAS exome AF: 0.575

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.130 AC: 189779 AN: 1457888 Hom.: 17616 Cov.: 30 AF XY: 0.132 AC XY: 95765 AN XY: 725268

African (AFR) AF: 0.0304 AC: 1013 AN: 33376

American (AMR) AF: 0.266 AC: 11729 AN: 44124

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3262 AN: 26104

East Asian (EAS) AF: 0.526 AC: 20755 AN: 39464

South Asian (SAS) AF: 0.227 AC: 19406 AN: 85620

European-Finnish (FIN) AF: 0.118 AC: 6284 AN: 53374

Middle Eastern (MID) AF: 0.0938 AC: 540 AN: 5756

European-Non Finnish (NFE) AF: 0.107 AC: 118391 AN: 1109834

Other (OTH) AF: 0.139 AC: 8399 AN: 60236

GnomAD4 genome AF: 0.119 AC: 18156 AN: 152224 Hom.: 1910 Cov.: 32 AF XY: 0.127 AC XY: 9417 AN XY: 74420

African (AFR) AF: 0.0357 AC: 1482 AN: 41542

American (AMR) AF: 0.202 AC: 3084 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 457 AN: 3470

East Asian (EAS) AF: 0.550 AC: 2851 AN: 5180

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1299 AN: 10594

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7388 AN: 68022

Other (OTH) AF: 0.135 AC: 285 AN: 2110

Alfa AF: 0.121 Hom.: 5659

Bravo AF: 0.124

TwinsUK AF: 0.111 AC: 412

ALSPAC AF: 0.108 AC: 416

ESP6500AA AF: 0.0389 AC: 144

ESP6500EA AF: 0.108 AC: 889

ExAC AF: 0.169 AC: 20394

Asia WGS AF: 0.344 AC: 1199 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

PIGB-related disorder Benign:1

Sep 13, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This 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
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.0031	T;T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.56	T;T;T
MetaRNN	Benign	0.00082	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.035	N;.;.
PhyloP100		2.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	1.1	N;N;.
REVEL	Benign	0.22
Sift	Benign	0.33	T;T;.
Sift4G	Benign	0.34	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.13
MPC		0.047
ClinPred		0.0032	T
GERP RS		3.2
Varity_R		0.060
gMVP		0.40
Mutation Taster		=94/6	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: rs2290344; hg19: chr15-55619796; COSMIC: COSV51241438;