rs886044116

Variant names:

• chr1-26794382-GA-AG
• rs886044116
• NM_017837.4:c.348_349delGAinsAG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_017837.4(PIGV):​c.348_349delGAinsAG​(p.Ile117Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L116L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIGV NM_017837.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3 B:2
• Conservation: PhyloP100: 0.325
• Publications: 0 publications found

Genes affected

PIGV (HGNC:26031): (phosphatidylinositol glycan anchor biosynthesis class V) This gene encodes a mannosyltransferase enzyme involved in the biosynthesis of glycosylphosphatidylinositol (GPI). GPI is a complex glycolipid that functions as a membrane anchor for many proteins and plays a role in multiple cellular processes including protein sorting and signal transduction. The encoded protein is localized to the endoplasmic reticulum and transfers the second mannose to the GPI backbone. Mutations in this gene are associated with hyperphosphatasia cognitive disability syndrome. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Feb 2011]

PIGV Gene-Disease associations (from GenCC):

• hyperphosphatasia with intellectual disability syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, ClinGen
• hyperphosphatasia-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 1-26794382-GA-AG is Benign according to our data. Variant chr1-26794382-GA-AG is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 289202.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017837.4. 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
	PIGV	NM_017837.4	MANE Select	c.348_349delGAinsAG	p.Ile117Val	missense	N/A	NP_060307.2
	PIGV	NM_001202554.2		c.348_349delGAinsAG	p.Ile117Val	missense	N/A	NP_001189483.1	Q9NUD9
	PIGV	NM_001374478.1		c.348_349delGAinsAG	p.Ile117Val	missense	N/A	NP_001361407.1	Q9NUD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIGV	ENST00000674202.1	MANE Select	c.348_349delGAinsAG	p.Ile117Val	missense	N/A	ENSP00000501479.1	Q9NUD9
	PIGV	ENST00000078527.9	TSL:1	c.348_349delGAinsAG	p.Ile117Val	missense	N/A	ENSP00000078527.4	Q9NUD9
	PIGV	ENST00000686325.1		c.348_349delGAinsAG	p.Ile117Val	missense	N/A	ENSP00000509836.1	A0A8I5KVW7

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	2	not provided (3)
-	2	-	Hyperphosphatasia with intellectual disability syndrome 1 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33

Splicing

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

Other links and lift over

dbSNP: rs886044116; hg19: chr1-27120873;