Variant chrX-48898423-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000218224.9(PQBP1):c.-87C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 982,613 control chromosomes in the GnomAD database, including 5 homozygotes. There are 747 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., 71 hem., cov: 22)

Exomes 𝑓: 0.0029 ( 5 hom. 676 hem. )

Consequence

PQBP1
ENST00000218224.9 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.49

Variant links:

Genes affected

PQBP1 (HGNC:9330): (polyglutamine binding protein 1) This gene encodes a nuclear polyglutamine-binding protein that is involved with transcription activation. The encoded protein contains a WW domain. Mutations in this gene have been found in patients with Renpenning syndrome 1 and other syndromes with X-linked cognitive disability. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.[provided by RefSeq, Nov 2009]

PQBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant X-48898423-C-T is Benign according to our data. Variant chrX-48898423-C-T is described in ClinVar as [Benign]. Clinvar id is 368452.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00218 (243/111701) while in subpopulation AMR AF= 0.00333 (35/10498). AF 95% confidence interval is 0.00246. There are 0 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 71 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PQBP1	NM_001032382.2 linkuse as main transcript	c.-18-69C>T		intron_variant		ENST00000447146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PQBP1	ENST00000447146.7 linkuse as main transcript	c.-18-69C>T		intron_variant		1	NM_001032382.2	P1	O60828-1

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

242

AN:

111648

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

AN XY:

33830

show subpopulations

Gnomad AFR

AF:

0.000619

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00492

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000369

Gnomad FIN

AF:

0.00751

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00239

Gnomad OTH

AF:

0.00133

GnomAD4 exome

AF:

0.00287

AC:

2499

AN:

870912

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

676

AN XY:

243750

show subpopulations

Gnomad4 AFR exome

AF:

0.000230

Gnomad4 AMR exome

AF:

0.000917

Gnomad4 ASJ exome

AF:

0.00608

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000478

Gnomad4 FIN exome

AF:

0.00870

Gnomad4 NFE exome

AF:

0.00294

Gnomad4 OTH exome

AF:

0.00254

GnomAD4 genome

AF:

0.00218

AC:

243

AN:

111701

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

AN XY:

33893

show subpopulations

Gnomad4 AFR

AF:

0.000618

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00492

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000370

Gnomad4 FIN

AF:

0.00751

Gnomad4 NFE

AF:

0.00241

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.00266

Hom.:

Bravo

AF:

0.00209

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Renpenning syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.18

DANN

Benign

0.89

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