X-48898494-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001032382.2(PQBP1):​c.-16C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 111,389 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Consequence

PQBP1
NM_001032382.2 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.139
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PQBP1NM_001032382.2 linkc.-16C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 2 of 7 ENST00000447146.7 NP_001027554.1 O60828-1A0A0S2Z4V5
PQBP1NM_001032382.2 linkc.-16C>T splice_region_variant Exon 2 of 7 ENST00000447146.7 NP_001027554.1 O60828-1A0A0S2Z4V5
PQBP1NM_001032382.2 linkc.-16C>T 5_prime_UTR_variant Exon 2 of 7 ENST00000447146.7 NP_001027554.1 O60828-1A0A0S2Z4V5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PQBP1ENST00000447146 linkc.-16C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 2 of 7 1 NM_001032382.2 ENSP00000391759.2 O60828-1
PQBP1ENST00000447146.7 linkc.-16C>T splice_region_variant Exon 2 of 7 1 NM_001032382.2 ENSP00000391759.2 O60828-1
PQBP1ENST00000447146 linkc.-16C>T 5_prime_UTR_variant Exon 2 of 7 1 NM_001032382.2 ENSP00000391759.2 O60828-1

Frequencies

GnomAD3 genomes
AF:
0.00000898
AC:
1
AN:
111389
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33569
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
29
GnomAD4 genome
AF:
0.00000898
AC:
1
AN:
111389
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33569
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 30, 2025
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Variant summary: PQBP1 c.-16C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 8.3e-07 in 1207520 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.-16C>T in individuals affected with Renpenning syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
CADD
Benign
11
DANN
Benign
0.88

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1321789163; hg19: chrX-48755777; API