rs606231198

Positions:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2

The NM_001032382.2(PQBP1):c.334_354delAGGGGCCATGACAAGTCGGAC(p.Arg112_Asp118del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000784 in 1,208,929 control chromosomes in the GnomAD database, including 3 homozygotes. There are 426 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00046 ( 1 hom., 17 hem., cov: 21)

Exomes 𝑓: 0.00082 ( 2 hom. 409 hem. )

Consequence

PQBP1
NM_001032382.2 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:6

Conservation

PhyloP100: 4.52

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:

PQBP1 (HGNC:):

PQBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001032382.2.

BP6

Variant X-48902256-AGCCATGACAAGTCGGACAGGG-A is Benign according to our data. Variant chrX-48902256-AGCCATGACAAGTCGGACAGGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 10984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000461 (51/110709) while in subpopulation SAS AF= 0.00698 (18/2578). AF 95% confidence interval is 0.00451. There are 1 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PQBP1	NM_001032382.2 linkuse as main transcript	c.334_354delAGGGGCCATGACAAGTCGGAC	p.Arg112_Asp118del	conservative_inframe_deletion	5/7	ENST00000447146.7	NP_001027554.1	O60828-1A0A0S2Z4V5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PQBP1	ENST00000447146.7 linkuse as main transcript	c.334_354delAGGGGCCATGACAAGTCGGAC	p.Arg112_Asp118del	conservative_inframe_deletion	5/7	1	NM_001032382.2	ENSP00000391759.2		O60828-1

Frequencies

GnomAD3 genomes

AF:

0.000461

AC:

AN:

110659

Hom.:

Cov.:

AF XY:

0.000516

AC XY:

AN XY:

32915

show subpopulations

Gnomad AFR

AF:

0.0000988

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00696

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000549

Gnomad OTH

AF:

0.000672

GnomAD3 exomes

AF:

0.000944

AC:

173

AN:

183289

Hom.:

AF XY:

0.00146

AC XY:

AN XY:

67777

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000219

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00646

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000513

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000817

AC:

897

AN:

1098220

Hom.:

AF XY:

0.00112

AC XY:

409

AN XY:

363584

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00728

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000544

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000461

AC:

AN:

110709

Hom.:

Cov.:

AF XY:

0.000516

AC XY:

AN XY:

32975

show subpopulations

Gnomad4 AFR

AF:

0.0000986

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00698

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000549

Gnomad4 OTH

AF:

0.000664

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.000423

EpiCase

AF:

0.000981

EpiControl

AF:

0.000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Renpenning syndrome

Pathogenic:1Benign:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Apr 01, 2006	- -
Likely benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 22, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 10, 2014	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 25, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2023	PQBP1: BS2 -

PQBP1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 08, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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