rs181088115

chrX-48903090-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001032382.2(PQBP1):c.*6C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000534 in 1,200,031 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 214 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., 27 hem., cov: 22)
  • Exomes 𝑓: 0.00052 (0 hom. 187 hem.)
• Consequence: PQBP1 NM_001032382.2 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: -1.91

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant X-48903090-C-T is Benign according to our data. Variant chrX-48903090-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 95308.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000651 (73/112214) while in subpopulation NFE AF= 0.00111 (59/53189). AF 95% confidence interval is 0.000882. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 27 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PQBP1	NM_001032382.2	c.*6C>T		3_prime_UTR_variant	7/7	ENST00000447146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PQBP1	ENST00000447146.7	c.*6C>T		3_prime_UTR_variant	7/7	1	NM_001032382.2	P1

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 73 AN: 112160 Hom.: 0 Cov.: 22 AF XY: 0.000787 AC XY: 27 AN XY: 34316

Gnomad AFR AF: 0.0000972

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000189

Gnomad ASJ AF: 0.000377

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000362

Gnomad FIN AF: 0.000980

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.00111

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000554 AC: 88 AN: 158986 Hom.: 0 AF XY: 0.000657 AC XY: 33 AN XY: 50250

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000156

Gnomad ASJ exome AF: 0.000862

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000241

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.000790

Gnomad OTH exome AF: 0.000497

GnomAD4 exome AF: 0.000522 AC: 568 AN: 1087817 Hom.: 0 Cov.: 33 AF XY: 0.000527 AC XY: 187 AN XY: 355171

Gnomad4 AFR exome AF: 0.0000381

Gnomad4 AMR exome AF: 0.000176

Gnomad4 ASJ exome AF: 0.00105

Gnomad4 EAS exome AF: 0.0000335

Gnomad4 SAS exome AF: 0.000268

Gnomad4 FIN exome AF: 0.00156

Gnomad4 NFE exome AF: 0.000494

Gnomad4 OTH exome AF: 0.00105

GnomAD4 genome AF: 0.000651 AC: 73 AN: 112214 Hom.: 0 Cov.: 22 AF XY: 0.000785 AC XY: 27 AN XY: 34380

Gnomad4 AFR AF: 0.0000970

Gnomad4 AMR AF: 0.000189

Gnomad4 ASJ AF: 0.000377

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000363

Gnomad4 FIN AF: 0.000980

Gnomad4 NFE AF: 0.00111

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000836 Hom.: 4

Bravo AF: 0.000552

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 05, 2020	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 03, 2014	- -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.19
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs181088115; hg19: chrX-48760367;