X-48904928-G-A

Variant names:

• chrX-48904928-G-A
• rs782603817
• NM_005660.3:c.981C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_005660.3(SLC35A2):​c.981C>T​(p.Gly327Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,096,825 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC35A2 NM_005660.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• SLC35A2-congenital disorder of glycosylation

  Inheritance: XL, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant X-48904928-G-A is Benign according to our data. Variant chrX-48904928-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 541108.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.2 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005660.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A2	NM_005660.3	MANE Select	c.981C>T	p.Gly327Gly	synonymous	Exon 4 of 5	NP_005651.1
	SLC35A2	NM_001282651.2		c.1065C>T	p.Gly355Gly	synonymous	Exon 5 of 5	NP_001269580.1
	SLC35A2	NM_001282650.2		c.1020C>T	p.Gly340Gly	synonymous	Exon 4 of 4	NP_001269579.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A2	ENST00000247138.11	TSL:1 MANE Select	c.981C>T	p.Gly327Gly	synonymous	Exon 4 of 5	ENSP00000247138.5
	SLC35A2	ENST00000376521.6	TSL:1	c.981C>T	p.Gly327Gly	synonymous	Exon 4 of 4	ENSP00000365704.1
	SLC35A2	ENST00000445167.7	TSL:1	c.427-36C>T		intron	N/A	ENSP00000402726.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 112076 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 179665 AF XY: 0.00

Gnomad AFR exome AF: 0.000155

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1096825 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 362223

African (AFR) AF: 0.0000758 AC: 2 AN: 26382

American (AMR) AF: 0.00 AC: 0 AN: 35123

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19364

East Asian (EAS) AF: 0.00 AC: 0 AN: 30186

South Asian (SAS) AF: 0.00 AC: 0 AN: 53946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40475

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841169

Other (OTH) AF: 0.00 AC: 0 AN: 46047

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 112129 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34299

African (AFR) AF: 0.00 AC: 0 AN: 30928

American (AMR) AF: 0.00 AC: 0 AN: 10604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3567

South Asian (SAS) AF: 0.00 AC: 0 AN: 2708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6125

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53126

Other (OTH) AF: 0.00 AC: 0 AN: 1522

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLC35A2-congenital disorder of glycosylation Benign:1

Jul 01, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.0
DANN	Benign	0.86
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs782603817; hg19: chrX-48762205; COSMIC: COSV104371210; COSMIC: COSV104371210;