rs741932

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong

The ENST00000474671.6(PQBP1):n.986C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 13103 hom., 18635 hem., cov: 22)

Exomes 𝑓: 0.61 ( 134857 hom. 222435 hem. )

Failed GnomAD Quality Control

Consequence

PQBP1
ENST00000474671.6 non_coding_transcript_exon

Scores

Splicing: ADA: 0.08010

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.58

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

Renpenning syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen
hamel cerebro-palato-cardiac syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked intellectual disability, Golabi-Ito-hall type
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked intellectual disability, Porteous type
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked intellectual disability, Sutherland-Haan type
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

PQBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant X-48901927-C-T is Benign according to our data. Variant chrX-48901927-C-T is described in ClinVar as Benign. ClinVar VariationId is 95309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PQBP1	NM_001032382.2 link	c.180-3C>T		splice_region_variant, intron_variant	Intron 3 of 6	ENST00000447146.7	NP_001027554.1	O60828-1A0A0S2Z4V5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PQBP1	ENST00000447146.7 link	c.180-3C>T		splice_region_variant, intron_variant	Intron 3 of 6	1	NM_001032382.2	ENSP00000391759.2		O60828-1

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

63578

AN:

109812

Hom.:

13112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.528

Gnomad AMI

AF:

0.762

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.600

Gnomad EAS

AF:

0.734

Gnomad SAS

AF:

0.751

Gnomad FIN

AF:

0.565

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.591

Gnomad OTH

AF:

0.585

GnomAD2 exomes

AF:

0.606

AC:

110628

AN:

182555

AF XY:

0.618

show subpopulations

Gnomad AFR exome

AF:

0.530

Gnomad AMR exome

AF:

0.525

Gnomad ASJ exome

AF:

0.612

Gnomad EAS exome

AF:

0.754

Gnomad FIN exome

AF:

0.584

Gnomad NFE exome

AF:

0.595

Gnomad OTH exome

AF:

0.602

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.607

AC:

666188

AN:

1097790

Hom.:

134857

Cov.:

AF XY:

0.612

AC XY:

222435

AN XY:

363180

show subpopulations

African (AFR)

AF:

0.531

AC:

14009

AN:

26395

American (AMR)

AF:

0.528

AC:

18578

AN:

35157

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

11904

AN:

19376

East Asian (EAS)

AF:

0.756

AC:

22819

AN:

30194

South Asian (SAS)

AF:

0.728

AC:

39410

AN:

54141

European-Finnish (FIN)

AF:

0.586

AC:

23691

AN:

40411

Middle Eastern (MID)

AF:

0.572

AC:

2366

AN:

4135

European-Non Finnish (NFE)

AF:

0.600

AC:

505360

AN:

841906

Other (OTH)

AF:

0.609

AC:

28051

AN:

46075

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

12974

25947

38921

51894

64868

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15860

31720

47580

63440

79300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.579

AC:

63595

AN:

109868

Hom.:

13103

Cov.:

AF XY:

0.579

AC XY:

18635

AN XY:

32204

show subpopulations

African (AFR)

AF:

0.528

AC:

15931

AN:

30176

American (AMR)

AF:

0.566

AC:

5823

AN:

10295

Ashkenazi Jewish (ASJ)

AF:

0.600

AC:

1580

AN:

2632

East Asian (EAS)

AF:

0.734

AC:

2547

AN:

3471

South Asian (SAS)

AF:

0.750

AC:

1926

AN:

2568

European-Finnish (FIN)

AF:

0.565

AC:

3265

AN:

5783

Middle Eastern (MID)

AF:

0.488

AC:

105

AN:

215

European-Non Finnish (NFE)

AF:

0.591

AC:

31048

AN:

52572

Other (OTH)

AF:

0.578

AC:

859

AN:

1485

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

983

1966

2948

3931

4914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.582

Hom.:

32138

Bravo

AF:

0.578

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Renpenning syndrome

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Oct 25, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

May 01, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

History of neurodevelopmental disorder

Benign:1

Mar 11, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.080

dbscSNV1_RF

Benign

0.23

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over