Variant chrX-48904831-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005660.3(SLC35A2):c.1078G>A(p.Val360Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,209,892 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 87 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., 16 hem., cov: 24)

Exomes 𝑓: 0.00013 ( 0 hom. 71 hem. )

Consequence

SLC35A2
NM_005660.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.175

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00741449).

BP6

Variant X-48904831-C-T is Benign according to our data. Variant chrX-48904831-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 509462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes 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.1078G>A	p.Val360Ile	missense_variant	4/5	ENST00000247138.11	NP_005651.1	P78381-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35A2	ENST00000247138.11 linkuse as main transcript	c.1078G>A	p.Val360Ile	missense_variant	4/5	1	NM_005660.3	ENSP00000247138.5		P78381-1

Frequencies

GnomAD3 genomes

AF:

0.000455

AC:

AN:

112162

Hom.:

Cov.:

AF XY:

0.000466

AC XY:

AN XY:

34334

show subpopulations

Gnomad AFR

AF:

0.00146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00110

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000259

AC:

AN:

181333

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

66117

show subpopulations

Gnomad AFR exome

AF:

0.00139

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00143

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000130

AC:

143

AN:

1097675

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

AN XY:

363053

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00154

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000831

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.000454

AC:

AN:

112217

Hom.:

Cov.:

AF XY:

0.000465

AC XY:

AN XY:

34399

show subpopulations

Gnomad4 AFR

AF:

0.00145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00111

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000137

Hom.:

Bravo

AF:

0.000487

ESP6500AA

AF:

0.00287

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000354

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2017

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. -

SLC35A2-congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

SLC35A2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-1.0

CADD

Benign

5.3

DANN

Benign

0.86

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.45

T;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.0074

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.81

N;N;N

REVEL

Benign

0.042

Sift

Benign

0.46

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.13

MVP

0.043

ClinPred

0.0059

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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