Variant rs35444896 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001321100.2(PGAP1):c.-578T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 1,613,862 control chromosomes in the GnomAD database, including 224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 117 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 107 hom. )

Consequence

PGAP1
NM_001321100.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.654

Variant links:

Genes affected

PGAP1 (HGNC:25712): (post-GPI attachment to proteins inositol deacylase 1) The protein encoded by this gene functions early in the glycosylphosphatidylinositol (GPI) biosynthetic pathway, catalyzing the inositol deacylation of GPI. The encoded protein is required for the production of GPI that can attach to proteins, and this may be an important factor in the transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi. Defects in this gene are a cause an autosomal recessive form of cognitive impairment. [provided by RefSeq, Jul 2017]

PGAP1 links:

PGAP1 (HGNC:):

PGAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 2-196912997-A-C is Benign according to our data. Variant chr2-196912997-A-C is described in ClinVar as [Benign]. Clinvar id is 474993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGAP1	NM_024989.4 linkuse as main transcript	c.534T>G	p.Leu178Leu	synonymous_variant	4/27	ENST00000354764.9	NP_079265.2	Q75T13-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGAP1	ENST00000354764.9 linkuse as main transcript	c.534T>G	p.Leu178Leu	synonymous_variant	4/27	1	NM_024989.4	ENSP00000346809.3		Q75T13-1

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3273

AN:

152174

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0737

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00618

AC:

1552

AN:

251054

Hom.:

AF XY:

0.00448

AC XY:

608

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.0774

Gnomad AMR exome

AF:

0.00528

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000704

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00268

AC:

3921

AN:

1461570

Hom.:

107

Cov.:

AF XY:

0.00238

AC XY:

1727

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.0779

Gnomad4 AMR exome

AF:

0.00629

Gnomad4 ASJ exome

AF:

0.000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000550

Gnomad4 OTH exome

AF:

0.00566

GnomAD4 genome

AF:

0.0216

AC:

3286

AN:

152292

Hom.:

117

Cov.:

AF XY:

0.0208

AC XY:

1548

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0738

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0122

Hom.:

Bravo

AF:

0.0244

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000655

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jun 23, 2017

- -

Intellectual disability, autosomal recessive 42

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.6

DANN

Benign

0.77

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

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