chr17-36537178-T-C

Position:

• chr17-36537178-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001346754.2(PIGW):​c.77T>C​(p.Leu26Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIGW NM_001346754.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.66

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-36537178-T-C is Pathogenic according to our data. Variant chr17-36537178-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 1704328.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.25140488). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGW	NM_001346754.2	c.77T>C	p.Leu26Ser	missense_variant	2/2	ENST00000614443.2	NP_001333683.1
PIGW	NM_001346755.2	c.77T>C	p.Leu26Ser	missense_variant	2/2		NP_001333684.1
PIGW	NM_178517.5	c.77T>C	p.Leu26Ser	missense_variant	2/2		NP_848612.2
MYO19	XM_047436823.1	c.-295-3074A>G		intron_variant			XP_047292779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGW	ENST00000614443.2	c.77T>C	p.Leu26Ser	missense_variant	2/2	1	NM_001346754.2	ENSP00000482202	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hyperphosphatasia with intellectual disability syndrome 5 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 08, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	.;T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.56	T;.;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	.;L;L
MutationTaster	Benign	0.86	D;D
PrimateAI	Benign	0.32	T
Sift4G	Benign	0.55	T;T;T
Polyphen		0.82	.;P;P
Vest4		0.22, 0.22
MutPred		0.55		Gain of glycosylation at L26 (P = 0.0672);Gain of glycosylation at L26 (P = 0.0672);Gain of glycosylation at L26 (P = 0.0672);
MVP		0.68
ClinPred		0.61	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-34893027;