Genetic Variant NM_001346754.2:c.5C>T (chr17-36537106-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001346754.2(PIGW):c.5C>T(p.Ser2Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PIGW
NM_001346754.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.55

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30332303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGW	NM_001346754.2 link	c.5C>T	p.Ser2Phe	missense_variant	Exon 2 of 2	ENST00000614443.2	NP_001333683.1	Q7Z7B1
PIGW	NM_001346755.2 link	c.5C>T	p.Ser2Phe	missense_variant	Exon 2 of 2		NP_001333684.1	Q7Z7B1
PIGW	NM_178517.5 link	c.5C>T	p.Ser2Phe	missense_variant	Exon 2 of 2		NP_848612.2	Q7Z7B1
MYO19	XM_047436823.1 link	c.-295-3002G>A		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.5C>T	p.Ser2Phe	missense_variant	Exon 2 of 2	1	NM_001346754.2	ENSP00000482202.1		Q7Z7B1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1431322

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.10e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

.;T;T

Eigen

Benign

0.026

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.40

T;.;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.8

.;M;M

PrimateAI

Uncertain

0.62

Sift4G

Benign

0.12

T;T;T

Polyphen

0.14

.;B;B

Vest4

0.14, 0.13

MutPred

0.30

Gain of stability (P = 0.0144);Gain of stability (P = 0.0144);Gain of stability (P = 0.0144);

MVP

0.40

ClinPred

0.84

GERP RS

4.8

Varity_R

0.11

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over