rs606231196

Variant names:

• chrX-48902788-GC-G
• NM_001032382.2:c.640delC

Your query was ambiguous. Multiple possible variants found:

• chrX-48902788-GC-G
• chrX-48902788-GC-GCC
• chrX-48902788-GC-GCCCCC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001032382.2(PQBP1):​c.640delC​(p.Arg214GlyfsTer62) variant causes a frameshift, splice region change. The variant allele was found at a frequency of 0.000000919 in 1,088,505 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: PQBP1 NM_001032382.2 frameshift, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.81

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 Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.198 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PQBP1	NM_001032382.2	c.640delC	p.Arg214GlyfsTer62	frameshift_variant, splice_region_variant	Exon 6 of 7	ENST00000447146.7	NP_001027554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PQBP1	ENST00000447146.7	c.640delC	p.Arg214GlyfsTer62	frameshift_variant, splice_region_variant	Exon 6 of 7	1	NM_001032382.2	ENSP00000391759.2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 9.19e-7 AC: 1 AN: 1088505 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 356215

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-48760065;