NM_001032382.2:c.*6C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001032382.2(PQBP1):c.*6C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000534 in 1,200,031 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 214 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., 27 hem., cov: 22)

Exomes 𝑓: 0.00052 ( 0 hom. 187 hem. )

Consequence

PQBP1
NM_001032382.2 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: -1.91

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]

PQBP1 links:

SLC35A2 (HGNC:11022): (solute carrier family 35 member A2) This gene encodes a member of the nucleotide-sugar transporter family. The encoded protein is a multi-pass membrane protein. It transports UDP-galactose from the cytosol into Golgi vesicles, where it serves as a glycosyl donor for the generation of glycans. Mutations in this gene cause congenital disorder of glycosylation type IIm (CDG2M). Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

SLC35A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-48903090-C-T is Benign according to our data. Variant chrX-48903090-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 95308.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000651 (73/112214) while in subpopulation NFE AF= 0.00111 (59/53189). AF 95% confidence interval is 0.000882. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 27 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PQBP1	NM_001032382.2 link	c.*6C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000447146.7	NP_001027554.1	O60828-1A0A0S2Z4V5
SLC35A2	NM_005660.3 link	c.*348G>A		downstream_gene_variant		ENST00000247138.11	NP_005651.1	P78381-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PQBP1	ENST00000447146.7 link	c.*6C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_001032382.2	ENSP00000391759.2		O60828-1
SLC35A2	ENST00000247138.11 link	c.*348G>A		downstream_gene_variant		1	NM_005660.3	ENSP00000247138.5		P78381-1

Frequencies

GnomAD3 genomes

AF:

0.000651

AC:

AN:

112160

Hom.:

Cov.:

AF XY:

0.000787

AC XY:

AN XY:

34316

show subpopulations

Gnomad AFR

AF:

0.0000972

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

Gnomad ASJ

AF:

0.000377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000362

Gnomad FIN

AF:

0.000980

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.00111

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000554

AC:

AN:

158986

Hom.:

AF XY:

0.000657

AC XY:

AN XY:

50250

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000156

Gnomad ASJ exome

AF:

0.000862

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000241

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.000790

Gnomad OTH exome

AF:

0.000497

GnomAD4 exome

AF:

0.000522

AC:

568

AN:

1087817

Hom.:

Cov.:

AF XY:

0.000527

AC XY:

187

AN XY:

355171

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

Gnomad4 AMR exome

AF:

0.000176

Gnomad4 ASJ exome

AF:

0.00105

Gnomad4 EAS exome

AF:

0.0000335

Gnomad4 SAS exome

AF:

0.000268

Gnomad4 FIN exome

AF:

0.00156

Gnomad4 NFE exome

AF:

0.000494

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.000651

AC:

AN:

112214

Hom.:

Cov.:

AF XY:

0.000785

AC XY:

AN XY:

34380

show subpopulations

Gnomad4 AFR

AF:

0.0000970

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.000377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000363

Gnomad4 FIN

AF:

0.000980

Gnomad4 NFE

AF:

0.00111

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000836

Hom.:

Bravo

AF:

0.000552

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Feb 05, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 03, 2014

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Uncertain:1

Jul 01, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.19

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over