X-48904753-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The ENST00000445167.7(SLC35A2):​c.566C>T​(p.Ser189Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,097,993 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

SLC35A2
ENST00000445167.7 missense

Scores

5
8

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.74
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22405341).
BP6
Variant X-48904753-G-A is Benign according to our data. Variant chrX-48904753-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1622521.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC35A2NM_005660.3 linkuse as main transcriptc.1156C>T p.Leu386= synonymous_variant 4/5 ENST00000247138.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC35A2ENST00000247138.11 linkuse as main transcriptc.1156C>T p.Leu386= synonymous_variant 4/51 NM_005660.3 P1P78381-1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
AF:
0.00000364
AC:
4
AN:
1097993
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
1
AN XY:
363353
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000475
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
24
Bravo
AF:
0.00000378

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMar 14, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
10
DANN
Uncertain
1.0
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.59
T;T;T
M_CAP
Uncertain
0.25
D
MetaRNN
Benign
0.22
T;T;T
MetaSVM
Benign
-0.89
T
MutationTaster
Benign
1.0
D;D;D;D;N;N;N
PROVEAN
Benign
-0.66
N;N;N
REVEL
Benign
0.13
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.042
D;D;D
Polyphen
0.0050
.;B;.
Vest4
0.33
MutPred
0.49
Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);.;
MVP
0.082
ClinPred
0.80
D
GERP RS
4.4

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs2063474261; hg19: chrX-48762030; API