17-36537248-T-C

Position:

• chr17-36537248-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001346754.2(PIGW):​c.147T>C​(p.Phe49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIGW NM_001346754.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.710

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 17-36537248-T-C is Benign according to our data. Variant chr17-36537248-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2099691.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.71 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGW	NM_001346754.2	c.147T>C	p.Phe49=	synonymous_variant	2/2	ENST00000614443.2
PIGW	NM_001346755.2	c.147T>C	p.Phe49=	synonymous_variant	2/2
PIGW	NM_178517.5	c.147T>C	p.Phe49=	synonymous_variant	2/2
MYO19	XM_047436823.1	c.-295-3144A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGW	ENST00000614443.2	c.147T>C	p.Phe49=	synonymous_variant	2/2	1	NM_001346754.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyperphosphatasia with intellectual disability syndrome 5 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.7
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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: chr17-34893097;