1-26787956-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_017837.4(PIGV):c.-370G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 152,460 control chromosomes in the GnomAD database, including 320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.056 (319 hom., cov: 32)
  • Exomes 𝑓: 0.075 (1 hom.)
• Consequence: PIGV NM_017837.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.98

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 1-26787956-G-A is Benign according to our data. Variant chr1-26787956-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 368873.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIGV	NM_017837.4	c.-370G>A		5_prime_UTR_variant	1/4	ENST00000674202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIGV	ENST00000674202.1	c.-370G>A		5_prime_UTR_variant	1/4		NM_017837.4	P1

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8595 AN: 152172 Hom.: 318 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.0197

Gnomad SAS AF: 0.0486

Gnomad FIN AF: 0.0832

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0540

GnomAD4 exome AF: 0.0747 AC: 13 AN: 174 Hom.: 1 Cov.: 0 AF XY: 0.0821 AC XY: 11 AN XY: 134

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0743

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0565 AC: 8601 AN: 152286 Hom.: 319 Cov.: 32 AF XY: 0.0563 AC XY: 4190 AN XY: 74476

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.0536

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.0195

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.0832

Gnomad4 NFE AF: 0.0795

Gnomad4 OTH AF: 0.0539

Alfa AF: 0.0642 Hom.: 48

Bravo AF: 0.0522

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyperphosphatasia-intellectual disability syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	19
Dann	Uncertain	0.98

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71636780; hg19: chr1-27114447;