rs370394797

chrX-48905348-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.561C>T(p.Ala187=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000717 in 1,185,535 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. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., 15 hem., cov: 24)
  • Exomes 𝑓: 0.000041 (0 hom. 7 hem.)
• Consequence: SLC35A2 NM_005660.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.27

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-48905348-G-A is Benign according to our data. Variant chrX-48905348-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 383300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.27 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A2	NM_005660.3	c.561C>T	p.Ala187=	synonymous_variant	4/5	ENST00000247138.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A2	ENST00000247138.11	c.561C>T	p.Ala187=	synonymous_variant	4/5	1	NM_005660.3	P1

Frequencies

GnomAD3 genomes AF: 0.000362 AC: 41 AN: 113312 Hom.: 0 Cov.: 24 AF XY: 0.000423 AC XY: 15 AN XY: 35456

Gnomad AFR AF: 0.00112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000184

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000278

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000562

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000104 AC: 14 AN: 134238 Hom.: 0 AF XY: 0.0000740 AC XY: 3 AN XY: 40564

Gnomad AFR exome AF: 0.00138

Gnomad AMR exome AF: 0.00

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: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000410 AC: 44 AN: 1072170 Hom.: 0 Cov.: 31 AF XY: 0.0000201 AC XY: 7 AN XY: 347682

Gnomad4 AFR exome AF: 0.00103

Gnomad4 AMR exome AF: 0.0000335

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: 0.00000964

Gnomad4 OTH exome AF: 0.000177

GnomAD4 genome AF: 0.000362 AC: 41 AN: 113365 Hom.: 0 Cov.: 24 AF XY: 0.000422 AC XY: 15 AN XY: 35519

Gnomad4 AFR AF: 0.00112

Gnomad4 AMR AF: 0.000184

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000279

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000562

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000427 Hom.: 0

Bravo AF: 0.000472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 06, 2018

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

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2016

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 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.21
Dann	Benign	0.85

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

Other links and lift over

dbSNP: rs370394797; hg19: chrX-48762625;