rs782276356

Variant names:

• chrX-48902429-C-G
• rs782276356
• NM_001032382.2:c.489C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-48902429-C-G
• chrX-48902429-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001032382.2(PQBP1):​c.489C>G​(p.Arg163Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 1,095,575 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R163R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000064 (0 hom. 5 hem.)
• Consequence: PQBP1 NM_001032382.2 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.17
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 5 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032382.2. 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.489C>G	p.Arg163Arg	synonymous	Exon 5 of 7	NP_001027554.1	O60828-1
	PQBP1	NM_001032381.2		c.489C>G	p.Arg163Arg	synonymous	Exon 5 of 7	NP_001027553.1	A0A0S2Z4V5
	PQBP1	NM_001032383.2		c.489C>G	p.Arg163Arg	synonymous	Exon 5 of 7	NP_001027555.1	O60828-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PQBP1	ENST00000447146.7	TSL:1 MANE Select	c.489C>G	p.Arg163Arg	synonymous	Exon 5 of 7	ENSP00000391759.2	O60828-1
	PQBP1	ENST00000218224.9	TSL:1	c.489C>G	p.Arg163Arg	synonymous	Exon 4 of 6	ENSP00000218224.4	O60828-1
	PQBP1	ENST00000463529.4	TSL:1	n.489C>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000639 AC: 7 AN: 1095575 Hom.: 0 Cov.: 35 AF XY: 0.0000138 AC XY: 5 AN XY: 361273

African (AFR) AF: 0.00 AC: 0 AN: 26391

American (AMR) AF: 0.00 AC: 0 AN: 34825

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19236

East Asian (EAS) AF: 0.00 AC: 0 AN: 30133

South Asian (SAS) AF: 0.00 AC: 0 AN: 53514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00000713 AC: 6 AN: 841037

Other (OTH) AF: 0.0000217 AC: 1 AN: 46025

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.7
DANN	Benign	0.83
PhyloP100		-5.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -45

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

Other links and lift over

dbSNP: rs782276356; hg19: chrX-48759706;