rs150603792

Variant names:

• chrX-48898423-C-T
• rs150603792
• ENST00000218224.9:c.-87C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005710.2(PQBP1):​c.-87C>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 0.00279 in 982,613 control chromosomes in the GnomAD database, including 5 homozygotes. There are 747 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., 71 hem., cov: 22)
  • Exomes 𝑓: 0.0029 (5 hom. 676 hem.)
• Consequence: PQBP1 NM_005710.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49
• Publications: 1 publications found

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: ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-48898423-C-T is Benign according to our data. Variant chrX-48898423-C-T is described in ClinVar as Benign. ClinVar VariationId is 368452.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00218 (243/111701) while in subpopulation AMR AF = 0.00333 (35/10498). AF 95% confidence interval is 0.00246. There are 0 homozygotes in GnomAd4. There are 71 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 71 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005710.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PQBP1	NM_001032382.2	MANE Select	c.-18-69C>T		intron	N/A	NP_001027554.1	O60828-1
	PQBP1	NM_005710.2		c.-87C>T		5_prime_UTR	Exon 1 of 6	NP_005701.1	A0A0S2Z4V5
	PQBP1	NM_001032381.2		c.-18-69C>T		intron	N/A	NP_001027553.1	A0A0S2Z4V5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PQBP1	ENST00000218224.9	TSL:1	c.-87C>T		5_prime_UTR	Exon 1 of 6	ENSP00000218224.4	O60828-1
	PQBP1	ENST00000447146.7	TSL:1 MANE Select	c.-18-69C>T		intron	N/A	ENSP00000391759.2	O60828-1
	PQBP1	ENST00000473764.6	TSL:1	n.339C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.00217 AC: 242 AN: 111648 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000619

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00492

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000369

Gnomad FIN AF: 0.00751

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00239

Gnomad OTH AF: 0.00133

GnomAD4 exome AF: 0.00287 AC: 2499 AN: 870912 Hom.: 5 Cov.: 15 AF XY: 0.00277 AC XY: 676 AN XY: 243750

African (AFR) AF: 0.000230 AC: 5 AN: 21734

American (AMR) AF: 0.000917 AC: 30 AN: 32701

Ashkenazi Jewish (ASJ) AF: 0.00608 AC: 108 AN: 17774

East Asian (EAS) AF: 0.00 AC: 0 AN: 28521

South Asian (SAS) AF: 0.000478 AC: 23 AN: 48097

European-Finnish (FIN) AF: 0.00870 AC: 345 AN: 39658

Middle Eastern (MID) AF: 0.00188 AC: 7 AN: 3716

European-Non Finnish (NFE) AF: 0.00294 AC: 1883 AN: 640113

Other (OTH) AF: 0.00254 AC: 98 AN: 38598

GnomAD4 genome AF: 0.00218 AC: 243 AN: 111701 Hom.: 0 Cov.: 22 AF XY: 0.00209 AC XY: 71 AN XY: 33893

African (AFR) AF: 0.000618 AC: 19 AN: 30761

American (AMR) AF: 0.00333 AC: 35 AN: 10498

Ashkenazi Jewish (ASJ) AF: 0.00492 AC: 13 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3571

South Asian (SAS) AF: 0.000370 AC: 1 AN: 2701

European-Finnish (FIN) AF: 0.00751 AC: 45 AN: 5989

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.00241 AC: 128 AN: 53118

Other (OTH) AF: 0.00131 AC: 2 AN: 1522

Alfa AF: 0.00266 Hom.: 15

Bravo AF: 0.00209

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Renpenning syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.18
DANN	Benign	0.89
PhyloP100		-1.5
PromoterAI		-0.0032	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs150603792; hg19: chrX-48755706;