rs61755368

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001346754.2(PIGW):c.705C>G(p.His235Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00826 in 1,614,112 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 66 hom. )

Consequence

PIGW
NM_001346754.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.996

Variant links:

Genes affected

PIGW (HGNC:23213): (phosphatidylinositol glycan anchor biosynthesis class W) The protein encoded by this gene is an inositol acyltransferase that acylates the inositol ring of phosphatidylinositol. This occurs in the endoplasmic reticulum and is a step in the biosynthesis of glycosylphosphatidylinositol (GPI), which anchors many cell surface proteins to the membrane. Defects in this gene are a cause of the age-dependent epileptic encephalopathy West syndrome as well as a syndrome exhibiting hyperphosphatasia and cognitive disability (HPMRS5). [provided by RefSeq, Jul 2017]

PIGW links:

MYO19 (HGNC:26234): (myosin XIX) Enables actin binding activity. Involved in regulation of cytokinesis and regulation of mitochondrial fission. Acts upstream of or within mitochondrion migration along actin filament. Located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

MYO19 links:

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 (MetaRNN=0.014726132).

BP6

Variant 17-36537806-C-G is Benign according to our data. Variant chr17-36537806-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 377070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00829 (1262/152294) while in subpopulation AMR AF= 0.0112 (172/15300). AF 95% confidence interval is 0.0105. There are 7 homozygotes in gnomad4. There are 668 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 rank	MANE	Protein	UniProt
PIGW	NM_001346754.2 link	c.705C>G	p.His235Gln	missense_variant	Exon 2 of 2	ENST00000614443.2	NP_001333683.1	Q7Z7B1
PIGW	NM_001346755.2 link	c.705C>G	p.His235Gln	missense_variant	Exon 2 of 2		NP_001333684.1	Q7Z7B1
PIGW	NM_178517.5 link	c.705C>G	p.His235Gln	missense_variant	Exon 2 of 2		NP_848612.2	Q7Z7B1
MYO19	XM_047436823.1 link	c.-295-3702G>C		intron_variant	Intron 2 of 29		XP_047292779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGW	ENST00000614443.2 link	c.705C>G	p.His235Gln	missense_variant	Exon 2 of 2	1	NM_001346754.2	ENSP00000482202.1		Q7Z7B1

Frequencies

GnomAD3 genomes

AF:

0.00829

AC:

1262

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00748

AC:

1875

AN:

250600

Hom.:

AF XY:

0.00717

AC XY:

974

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.00165

Gnomad AMR exome

AF:

0.00457

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0266

Gnomad NFE exome

AF:

0.00917

Gnomad OTH exome

AF:

0.00789

GnomAD4 exome

AF:

0.00826

AC:

12078

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00813

AC XY:

5915

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00449

Gnomad4 ASJ exome

AF:

0.00337

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.0244

Gnomad4 NFE exome

AF:

0.00906

Gnomad4 OTH exome

AF:

0.00616

GnomAD4 genome

AF:

0.00829

AC:

1262

AN:

152294

Hom.:

Cov.:

AF XY:

0.00897

AC XY:

668

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0245

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00557

Hom.:

Bravo

AF:

0.00558

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00698

AC:

ExAC

AF:

0.00695

AC:

844

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00780

EpiControl

AF:

0.00788

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PIGW: BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 30, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 25, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28327575) -

Hyperphosphatasia with intellectual disability syndrome 5

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Pathogenic

0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

.;T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

D;.;T

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Uncertain

-0.057

MutationAssessor

Pathogenic

3.7

.;H;H

PrimateAI

Uncertain

0.65

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.95, 0.95

MutPred

0.92

Gain of catalytic residue at H235 (P = 0.1155);Gain of catalytic residue at H235 (P = 0.1155);Gain of catalytic residue at H235 (P = 0.1155);

MVP

0.40

ClinPred

0.067

GERP RS

2.7

Varity_R

0.27

gMVP

0.87

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