rs606231198

chrX-48902256-AGCCATGACAAGTCGGACAGGG-AchrX-48902256-AGCCATGACAAGTCGGACAGGG-AGCCATGACAAGTCGGACAGGGGCCATGACAAGTCGGACAGGG

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BS1 BS2

The NM_001032382.2(PQBP1):c.334_354del(p.Gly113_Arg119del) variant causes a 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 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:6
• Conservation: PhyloP100: 4.52

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PQBP1	NM_001032382.2	c.334_354del	p.Gly113_Arg119del	inframe_deletion	5/7	ENST00000447146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PQBP1	ENST00000447146.7	c.334_354del	p.Gly113_Arg119del	inframe_deletion	5/7	1	NM_001032382.2	P1

Frequencies

GnomAD3 genomes AF: 0.000461 AC: 51 AN: 110659 Hom.: 1 Cov.: 21 AF XY: 0.000516 AC XY: 17 AN XY: 32915

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.: 0 AF XY: 0.00146 AC XY: 99 AN XY: 67777

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.: 2 AF XY: 0.00112 AC XY: 409 AN XY: 363584

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: 51 AN: 110709 Hom.: 1 Cov.: 21 AF XY: 0.000516 AC XY: 17 AN XY: 32975

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.: 2

Bravo AF: 0.000423

EpiCase AF: 0.000981

EpiControl AF: 0.000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1 Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Renpenning syndrome Pathogenic:1 Benign: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

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

PQBP1-related condition Benign:1

Likely benign, criteria provided, single submitter

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs606231198; hg19: chrX-48759533;