rs181088115

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000474671.6(PQBP1):n.1959C>T variant causes a non coding transcript exon 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
ENST00000474671.6 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.91

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

SLC35A2-congenital disorder of glycosylation
Inheritance: XL, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

SLC35A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 95308.

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 the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

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.:

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

GnomAD2 exomes

AF:

0.000554

AC:

AN:

158986

AF XY:

0.000657

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 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

African (AFR)

AF:

0.0000381

AC:

AN:

26269

American (AMR)

AF:

0.000176

AC:

AN:

34000

Ashkenazi Jewish (ASJ)

AF:

0.00105

AC:

AN:

19091

East Asian (EAS)

AF:

0.0000335

AC:

AN:

29889

South Asian (SAS)

AF:

0.000268

AC:

AN:

52306

European-Finnish (FIN)

AF:

0.00156

AC:

AN:

39641

Middle Eastern (MID)

AF:

0.000730

AC:

AN:

4108

European-Non Finnish (NFE)

AF:

0.000494

AC:

413

AN:

836803

Other (OTH)

AF:

0.00105

AC:

AN:

45710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000651

AC:

AN:

112214

Hom.:

Cov.:

AF XY:

0.000785

AC XY:

AN XY:

34380

show subpopulations

African (AFR)

AF:

0.0000970

AC:

AN:

30938

American (AMR)

AF:

0.000189

AC:

AN:

10581

Ashkenazi Jewish (ASJ)

AF:

0.000377

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3559

South Asian (SAS)

AF:

0.000363

AC:

AN:

2752

European-Finnish (FIN)

AF:

0.000980

AC:

AN:

6122

Middle Eastern (MID)

AF:

0.00457

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00111

AC:

AN:

53189

Other (OTH)

AF:

0.00

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.74

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over