chrX-48905057-C-A

Variant names:

• chrX-48905057-C-A
• rs782161189
• NM_005660.3:c.852G>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.852G>T​(p.Leu284Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,097,533 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000046 (0 hom. 1 hem.)
• Consequence: SLC35A2 NM_005660.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.382
• 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: Ambry Genetics, G2P, Orphanet, Illumina, PanelApp Australia, 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=-0.55).
• BP6: Variant X-48905057-C-A is Benign according to our data. Variant chrX-48905057-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 541106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.382 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A2	NM_005660.3	MANE Select	c.852G>T	p.Leu284Leu	synonymous	Exon 4 of 5	NP_005651.1	P78381-1
	SLC35A2	NM_001282651.2		c.936G>T	p.Leu312Leu	synonymous	Exon 5 of 5	NP_001269580.1	P78381-4
	SLC35A2	NM_001282650.2		c.891G>T	p.Leu297Leu	synonymous	Exon 4 of 4	NP_001269579.1	B4DE15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A2	ENST00000247138.11	TSL:1 MANE Select	c.852G>T	p.Leu284Leu	synonymous	Exon 4 of 5	ENSP00000247138.5	P78381-1
	SLC35A2	ENST00000376521.6	TSL:1	c.852G>T	p.Leu284Leu	synonymous	Exon 4 of 4	ENSP00000365704.1	P78381-2
	SLC35A2	ENST00000445167.7	TSL:1	c.427-165G>T		intron	N/A	ENSP00000402726.2	P78381-3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000277 AC: 5 AN: 180816 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000183

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: 0.00000456 AC: 5 AN: 1097533 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362907

African (AFR) AF: 0.00 AC: 0 AN: 26385

American (AMR) AF: 0.000142 AC: 5 AN: 35178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19373

East Asian (EAS) AF: 0.00 AC: 0 AN: 30185

South Asian (SAS) AF: 0.00 AC: 0 AN: 54060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40493

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841675

Other (OTH) AF: 0.00 AC: 0 AN: 46050

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	SLC35A2-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.8
DANN	Benign	0.77
PhyloP100		0.38
Mutation Taster		=97/3	polymorphism

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: rs782161189; hg19: chrX-48762334;