rs782301792

chrX-48905270-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.639C>T(p.Ser213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,198,202 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 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 0.000053 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.000032 (0 hom. 12 hem.)
• Consequence: SLC35A2 NM_005660.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.50

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=-0.88).
• BP6: Variant X-48905270-G-A is Benign according to our data. Variant chrX-48905270-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 541109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.5 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A2	NM_005660.3	c.639C>T	p.Ser213=	synonymous_variant	4/5	ENST00000247138.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A2	ENST00000247138.11	c.639C>T	p.Ser213=	synonymous_variant	4/5	1	NM_005660.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000531 AC: 6 AN: 112992 Hom.: 0 Cov.: 24 AF XY: 0.0000570 AC XY: 2 AN XY: 35116

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000930

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000832

Gnomad SAS AF: 0.000358

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000981 AC: 15 AN: 152887 Hom.: 0 AF XY: 0.0000656 AC XY: 3 AN XY: 45763

Gnomad AFR exome AF: 0.0000925

Gnomad AMR exome AF: 0.0000813

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000333

Gnomad SAS exome AF: 0.000376

Gnomad FIN exome AF: 0.0000732

Gnomad NFE exome AF: 0.0000153

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000323 AC: 35 AN: 1085160 Hom.: 0 Cov.: 31 AF XY: 0.0000340 AC XY: 12 AN XY: 353120

Gnomad4 AFR exome AF: 0.0000764

Gnomad4 AMR exome AF: 0.0000597

Gnomad4 ASJ exome AF: 0.0000527

Gnomad4 EAS exome AF: 0.000168

Gnomad4 SAS exome AF: 0.000229

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.0000878

GnomAD4 genome AF: 0.0000531 AC: 6 AN: 113042 Hom.: 0 Cov.: 24 AF XY: 0.0000569 AC XY: 2 AN XY: 35176

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000929

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000835

Gnomad4 SAS AF: 0.000359

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000718

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2017

This alteration is classified as likely 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

Invitae

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.53
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs782301792; hg19: chrX-48762547;