X-48904951-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_ModerateBP6_ModerateBS2

The NM_005660.3(SLC35A2):c.958G>A(p.Val320Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000537 in 1,209,466 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V320L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.000055 ( 0 hom. 20 hem. )

Consequence

SLC35A2
NM_005660.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.11

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 Likely_benign. Variant got -6 ACMG points.

PM1

In a transmembrane_region Helical (size 20) in uniprot entity S35A2_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_005660.3

BP4

Computational evidence support a benign effect (MetaRNN=0.16560423).

BP6

Variant X-48904951-C-T is Benign according to our data. Variant chrX-48904951-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1578345.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A2	NM_005660.3 linkuse as main transcript	c.958G>A	p.Val320Met	missense_variant	4/5	ENST00000247138.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A2	ENST00000247138.11 linkuse as main transcript	c.958G>A	p.Val320Met	missense_variant	4/5	1	NM_005660.3	P1	P78381-1

Frequencies

GnomAD3 genomes

AF:

0.0000446

AC:

AN:

112084

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34262

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000942

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000753

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000388

AC:

AN:

180637

Hom.:

AF XY:

0.0000306

AC XY:

AN XY:

65339

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000746

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1097382

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

362762

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000654

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000446

AC:

AN:

112084

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000942

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000753

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SLC35A2-congenital disorder of glycosylation

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 22, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.33

T;.;.;T;.

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.96

D;D;D;D;D

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.17

T;T;T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.6

L;L;.;.;.

MutationTaster

Benign

0.98

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.49

N;N;.;.;N

REVEL

Benign

0.13

Sift

Benign

0.19

T;T;.;.;T

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.17

B;P;.;P;.

Vest4

0.36

MVP

0.27

MPC

1.0

ClinPred

0.11

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.094

gMVP

0.70

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