X-48902337-C-G

Position:

• chrX-48902337-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001032382.2(PQBP1):​c.397C>G​(p.Arg133Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000021 in 1,097,431 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000021 (0 hom. 7 hem.)
• Consequence: PQBP1 NM_001032382.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23090246).
• BS2: High Hemizygotes in GnomAdExome4 at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PQBP1	NM_001032382.2	c.397C>G	p.Arg133Gly	missense_variant	5/7	ENST00000447146.7	NP_001027554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PQBP1	ENST00000447146.7	c.397C>G	p.Arg133Gly	missense_variant	5/7	1	NM_001032382.2	ENSP00000391759.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000553 AC: 1 AN: 180762 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 65630

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000210 AC: 23 AN: 1097431 Hom.: 0 Cov.: 35 AF XY: 0.0000193 AC XY: 7 AN XY: 362963

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: 0.0000261

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 22

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T;T;T;T;.
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.82	T;.;.;.;.
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.90	L;L;L;L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Uncertain	0.39
Sift	Benign	0.092	T;T;T;T;T
Sift4G	Benign	0.33	T;T;T;T;T
Polyphen		0.99	D;D;D;D;.
Vest4		0.69
MutPred		0.39		Loss of MoRF binding (P = 0.0033);Loss of MoRF binding (P = 0.0033);Loss of MoRF binding (P = 0.0033);Loss of MoRF binding (P = 0.0033);Loss of MoRF binding (P = 0.0033);
MVP		0.90
MPC		0.97
ClinPred		0.26	T
GERP RS		4.7
Varity_R		0.23

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: rs201489630; hg19: chrX-48759614;