Variant chr1-26787956-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.98

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
PIGV	NM_017837.4 linkuse as main transcript	c.-370G>A		5_prime_UTR_variant	1/4	ENST00000674202.1	NP_060307.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGV	ENST00000674202.1 linkuse as main transcript	c.-370G>A		5_prime_UTR_variant	1/4		NM_017837.4	ENSP00000501479	P1

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8595

AN:

152172

Hom.:

318

Cov.:

show subpopulations

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:

AN:

174

Hom.:

Cov.:

AF XY:

0.0821

AC XY:

AN XY:

134

show subpopulations

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.:

AF XY:

0.0563

AC XY:

4190

AN XY:

74476

show subpopulations

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.:

Bravo

AF:

0.0522

Asia WGS

AF:

0.0390

AC:

136

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hyperphosphatasia-intellectual disability syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over