X-48911594-G-T

Position:

chrX-48911594-G-T

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 380583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-48911594-G-T is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35A2	NM_005660.3 linkuse as main transcript	c.43C>A	p.Pro15Thr	missense_variant	1/5	ENST00000247138.11	NP_005651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35A2	ENST00000247138.11 linkuse as main transcript	c.43C>A	p.Pro15Thr	missense_variant	1/5	1	NM_005660.3	ENSP00000247138	P1	P78381-1

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

1740

AN:

113199

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

530

AN XY:

35347

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

GnomAD3 exomes

AF:

0.0161

AC:

1732

AN:

107447

Hom.:

AF XY:

0.0153

AC XY:

567

AN XY:

36957

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 SAS exome

AF:

0.00771

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

Gnomad4 AFR exome

AF:

0.00260

Gnomad4 AMR exome

AF:

0.00806

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.0000730

Gnomad4 SAS exome

AF:

0.00715

Gnomad4 FIN exome

AF:

0.0283

Gnomad4 NFE exome

AF:

0.0261

Gnomad4 OTH exome

AF:

0.0221

GnomAD4 genome

AF:

0.0154

AC:

1741

AN:

113251

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

532

AN XY:

35409

show subpopulations

Gnomad4 AFR

AF:

0.00374

Gnomad4 AMR

AF:

0.0102

Gnomad4 ASJ

AF:

0.00942

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00746

Gnomad4 FIN

AF:

0.0258

Gnomad4 NFE

AF:

0.0238

Gnomad4 OTH

AF:

0.0174

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

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 30, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 26, 2016

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

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2016

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

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

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;.;.;.;.;.

MutationTaster

Benign

1.0

D;N;N;N;N;N;N;N

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

Polyphen

0.22

B;.;B;B;.;B;.;.;.;B;.;.

Vest4

0.14

MPC

1.0

ClinPred

0.0011

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.33

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

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