Variant X-48898207-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000218224.9(PQBP1):c.-303G>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 0.0142 in 986,599 control chromosomes in the GnomAD database, including 92 homozygotes. There are 3,804 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 11 hom., 285 hem., cov: 23)

Exomes 𝑓: 0.015 ( 81 hom. 3519 hem. )

Consequence

PQBP1
ENST00000218224.9 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.723

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-48898207-G-T is Benign according to our data. Variant chrX-48898207-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 677296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00998 (1122/112454) while in subpopulation NFE AF= 0.0155 (825/53259). AF 95% confidence interval is 0.0146. There are 11 homozygotes in gnomad4. There are 285 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PQBP1	NM_001032382.2 linkuse as main transcript	c.-19+125G>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.-19+125G>T		intron_variant		1	NM_001032382.2	P1	O60828-1

Frequencies

GnomAD3 genomes

AF:

0.00999

AC:

1123

AN:

112401

Hom.:

Cov.:

AF XY:

0.00825

AC XY:

285

AN XY:

34549

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.0589

Gnomad AMR

AF:

0.00752

Gnomad ASJ

AF:

0.0313

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00357

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.00858

GnomAD4 exome

AF:

0.0147

AC:

12891

AN:

874145

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

3519

AN XY:

222609

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00441

Gnomad4 ASJ exome

AF:

0.0293

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000548

Gnomad4 FIN exome

AF:

0.00455

Gnomad4 NFE exome

AF:

0.0173

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.00998

AC:

1122

AN:

112454

Hom.:

Cov.:

AF XY:

0.00823

AC XY:

285

AN XY:

34612

show subpopulations

Gnomad4 AFR

AF:

0.00187

Gnomad4 AMR

AF:

0.00751

Gnomad4 ASJ

AF:

0.0313

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00357

Gnomad4 NFE

AF:

0.0155

Gnomad4 OTH

AF:

0.00847

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.00975

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.4

DANN

Benign

0.48

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