chrX-48911594-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005660.3(SLC35A2):c.43C>A(p.Pro15Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,163,770 control chromosomes in the GnomAD database, including 226 homozygotes. There are 8,200 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 16 hom., 532 hem., cov: 25)

Exomes 𝑓: 0.023 ( 210 hom. 7668 hem. )

Consequence

SLC35A2
NM_005660.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.345

Publications

4 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 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017829537).

BP6

Variant X-48911594-G-T is Benign according to our data. Variant chrX-48911594-G-T is described in ClinVar as Benign. ClinVar VariationId is 380583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0154 (1741/113251) while in subpopulation NFE AF = 0.0238 (1268/53268). AF 95% confidence interval is 0.0227. There are 16 homozygotes in GnomAd4. There are 532 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A2	NM_005660.3 link	c.43C>A	p.Pro15Thr	missense_variant	Exon 1 of 5	ENST00000247138.11	NP_005651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A2	ENST00000247138.11 link	c.43C>A	p.Pro15Thr	missense_variant	Exon 1 of 5	1	NM_005660.3	ENSP00000247138.5

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

1740

AN:

113199

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00374

Gnomad AMI

AF:

0.00733

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.00942

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00708

Gnomad FIN

AF:

0.0258

Gnomad MID

AF:

0.0167

Gnomad NFE

AF:

0.0238

Gnomad OTH

AF:

0.0176

GnomAD2 exomes

AF:

0.0161

AC:

1732

AN:

107447

AF XY:

0.0153

show subpopulations

Gnomad AFR exome

AF:

0.00410

Gnomad AMR exome

AF:

0.00800

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0310

Gnomad NFE exome

AF:

0.0261

Gnomad OTH exome

AF:

0.0143

GnomAD4 exome

AF:

0.0231

AC:

24234

AN:

1050519

Hom.:

210

Cov.:

AF XY:

0.0224

AC XY:

7668

AN XY:

342897

show subpopulations

African (AFR)

AF:

0.00260

AC:

AN:

25015

American (AMR)

AF:

0.00806

AC:

233

AN:

28924

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

221

AN:

18655

East Asian (EAS)

AF:

0.0000730

AC:

AN:

27409

South Asian (SAS)

AF:

0.00715

AC:

358

AN:

50065

European-Finnish (FIN)

AF:

0.0283

AC:

877

AN:

30984

Middle Eastern (MID)

AF:

0.0138

AC:

AN:

3540

European-Non Finnish (NFE)

AF:

0.0261

AC:

21448

AN:

821541

Other (OTH)

AF:

0.0221

AC:

981

AN:

44386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

957

1914

2871

3828

4785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.0154

AC:

1741

AN:

113251

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

532

AN XY:

35409

show subpopulations

African (AFR)

AF:

0.00374

AC:

117

AN:

31319

American (AMR)

AF:

0.0102

AC:

111

AN:

10848

Ashkenazi Jewish (ASJ)

AF:

0.00942

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3578

South Asian (SAS)

AF:

0.00746

AC:

AN:

2814

European-Finnish (FIN)

AF:

0.0258

AC:

163

AN:

6316

Middle Eastern (MID)

AF:

0.0183

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0238

AC:

1268

AN:

53268

Other (OTH)

AF:

0.0174

AC:

AN:

1554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

139

209

278

348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0191

Hom.:

144

Bravo

AF:

0.0136

TwinsUK

AF:

0.0237

AC:

ALSPAC

AF:

0.0239

AC:

ESP6500AA

AF:

0.00172

AC:

ESP6500EA

AF:

0.0212

AC:

130

ExAC

AF:

0.0126

AC:

1245

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

Sep 30, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Jan 26, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Inborn genetic diseases

Benign:1

May 03, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

SLC35A2-congenital disorder of glycosylation

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.8

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.16

T;.;.;.;.;T;.;T;T;T;T;.

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.87

D;D;D;D;T;D;T;T;D;D;D;T

MetaRNN

Benign

0.0018

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;N;N;N;.;N;.;.;.;.;.

PhyloP100

0.34

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.32

N;N;N;N;.;.;N;.;.;.;N;.

REVEL

Benign

0.023

Sift

Benign

0.033

D;D;T;D;.;.;D;.;.;.;D;.

Sift4G

Benign

0.23

T;T;T;T;D;T;T;.;T;T;T;D

Vest4

0.14

ClinPred

0.0011

GERP RS

2.1

PromoterAI

-0.047

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.33

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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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