rs146079657

Positions:

• chrX-48904919-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005660.3(SLC35A2):​c.990C>T​(p.Leu330=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000867 in 1,208,994 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 361 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., 27 hem., cov: 23)
  • Exomes 𝑓: 0.00089 (0 hom. 334 hem.)
• Consequence: SLC35A2 NM_005660.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.292

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant X-48904919-G-A is Benign according to our data. Variant chrX-48904919-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 383041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.292 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 27 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A2	NM_005660.3	c.990C>T	p.Leu330=	synonymous_variant	4/5	ENST00000247138.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A2	ENST00000247138.11	c.990C>T	p.Leu330=	synonymous_variant	4/5	1	NM_005660.3	P1

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 73 AN: 112132 Hom.: 0 Cov.: 23 AF XY: 0.000788 AC XY: 27 AN XY: 34278

Gnomad AFR AF: 0.0000648

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000189

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000163

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.00199

GnomAD3 exomes AF: 0.000567 AC: 102 AN: 180043 Hom.: 0 AF XY: 0.000695 AC XY: 45 AN XY: 64769

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000184

Gnomad ASJ exome AF: 0.000673

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000107

Gnomad FIN exome AF: 0.000322

Gnomad NFE exome AF: 0.00102

Gnomad OTH exome AF: 0.000672

GnomAD4 exome AF: 0.000889 AC: 975 AN: 1096862 Hom.: 0 Cov.: 31 AF XY: 0.000922 AC XY: 334 AN XY: 362242

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.000228

Gnomad4 ASJ exome AF: 0.000516

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000556

Gnomad4 FIN exome AF: 0.000297

Gnomad4 NFE exome AF: 0.00106

Gnomad4 OTH exome AF: 0.000999

GnomAD4 genome AF: 0.000651 AC: 73 AN: 112132 Hom.: 0 Cov.: 23 AF XY: 0.000788 AC XY: 27 AN XY: 34278

Gnomad4 AFR AF: 0.0000648

Gnomad4 AMR AF: 0.000189

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000163

Gnomad4 NFE AF: 0.00122

Gnomad4 OTH AF: 0.00199

Alfa AF: 0.000972 Hom.: 7

Bravo AF: 0.000438

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

SLC35A2-congenital disorder of glycosylation Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 17, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 09, 2023	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 17, 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

Apr 18, 2017

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.5
DANN	Benign	0.86
BranchPoint Hunter		0.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs146079657; hg19: chrX-48762196; COSMIC: COSV54430150; COSMIC: COSV54430150;