ENST00000376521.6:c.*1211G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000376521.6(SLC35A2):c.*1211G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 563,315 control chromosomes in the GnomAD database, including 32,580 homozygotes. There are 82,019 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 6467 hom., 13117 hem., cov: 23)

Exomes 𝑓: 0.42 ( 26113 hom. 68902 hem. )

Consequence

SLC35A2
ENST00000376521.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.433

Publications

6 publications found

Variant links:

Genes affected

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:

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen
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

PQBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-48903516-C-T is Benign according to our data. Variant chrX-48903516-C-T is described in ClinVar as [Benign]. Clinvar id is 1245601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A2	NM_005660.3 link	c.1164-51G>A		intron_variant	Intron 4 of 4	ENST00000247138.11	NP_005651.1	P78381-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A2	ENST00000247138.11 link	c.1164-51G>A		intron_variant	Intron 4 of 4	1	NM_005660.3	ENSP00000247138.5		P78381-1

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

44632

AN:

110316

Hom.:

6466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.724

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.406

Gnomad MID

AF:

0.401

Gnomad NFE

AF:

0.410

Gnomad OTH

AF:

0.401

GnomAD2 exomes

AF:

0.416

AC:

66787

AN:

160412

AF XY:

0.418

show subpopulations

Gnomad AFR exome

AF:

0.377

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.619

Gnomad FIN exome

AF:

0.425

Gnomad NFE exome

AF:

0.418

Gnomad OTH exome

AF:

0.419

GnomAD4 exome

AF:

0.421

AC:

190711

AN:

452946

Hom.:

26113

Cov.:

AF XY:

0.424

AC XY:

68902

AN XY:

162638

show subpopulations

African (AFR)

AF:

0.371

AC:

5190

AN:

13979

American (AMR)

AF:

0.356

AC:

11707

AN:

32923

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

5699

AN:

15107

East Asian (EAS)

AF:

0.622

AC:

16783

AN:

26980

South Asian (SAS)

AF:

0.397

AC:

16012

AN:

40347

European-Finnish (FIN)

AF:

0.425

AC:

16815

AN:

39519

Middle Eastern (MID)

AF:

0.407

AC:

1227

AN:

3017

European-Non Finnish (NFE)

AF:

0.417

AC:

106844

AN:

256311

Other (OTH)

AF:

0.421

AC:

10434

AN:

24763

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

3935

7869

11804

15738

19673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.404

AC:

44642

AN:

110369

Hom.:

6467

Cov.:

AF XY:

0.402

AC XY:

13117

AN XY:

32661

show subpopulations

African (AFR)

AF:

0.375

AC:

11392

AN:

30397

American (AMR)

AF:

0.389

AC:

4048

AN:

10410

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

967

AN:

2633

East Asian (EAS)

AF:

0.599

AC:

2087

AN:

3487

South Asian (SAS)

AF:

0.406

AC:

1051

AN:

2586

European-Finnish (FIN)

AF:

0.406

AC:

2383

AN:

5869

Middle Eastern (MID)

AF:

0.389

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.410

AC:

21553

AN:

52608

Other (OTH)

AF:

0.397

AC:

595

AN:

1497

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

982

1965

2947

3930

4912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.406

Hom.:

36645

Bravo

AF:

0.406

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 23, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

0.43

Mutation Taster

=100/0

polymorphism (auto)

(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

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ENST00000376521.6:c.*1211G>A

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