17-36537155-C-T

Variant names:

• chr17-36537155-C-T
• rs529378174
• NM_001346754.2:c.54C>T

Variant summary

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

The NM_001346754.2(PIGW):​c.54C>T​(p.Thr18Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T18T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: PIGW NM_001346754.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 17-36537155-C-T is Benign according to our data. Variant chr17-36537155-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1099021.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.44 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346754.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGW	NM_001346754.2	MANE Select	c.54C>T	p.Thr18Thr	synonymous	Exon 2 of 2	NP_001333683.1	Q7Z7B1
	PIGW	NM_001346755.2		c.54C>T	p.Thr18Thr	synonymous	Exon 2 of 2	NP_001333684.1	Q7Z7B1
	PIGW	NM_178517.5		c.54C>T	p.Thr18Thr	synonymous	Exon 2 of 2	NP_848612.2	Q7Z7B1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGW	ENST00000614443.2	TSL:1 MANE Select	c.54C>T	p.Thr18Thr	synonymous	Exon 2 of 2	ENSP00000482202.1	Q7Z7B1
	PIGW	ENST00000619326.1	TSL:1	c.54C>T	p.Thr18Thr	synonymous	Exon 2 of 2	ENSP00000480475.1	A0A087WWS9
	PIGW	ENST00000620233.1	TSL:2	c.54C>T	p.Thr18Thr	synonymous	Exon 2 of 2	ENSP00000480021.1	Q7Z7B1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000800 AC: 2 AN: 250072 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460760 Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6 AN XY: 726642

African (AFR) AF: 0.00 AC: 0 AN: 33412

American (AMR) AF: 0.0000450 AC: 2 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 85988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111634

Other (OTH) AF: 0.0000331 AC: 2 AN: 60352

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74480

African (AFR) AF: 0.0000240 AC: 1 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hyperphosphatasia with intellectual disability syndrome 5 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.3
DANN	Benign	0.64
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs529378174; hg19: chr17-34893004;