chrX-48905159-G-C

Variant names:

• chrX-48905159-G-C
• rs375311728
• NM_005660.3:c.750C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005660.3(SLC35A2):​c.750C>G​(p.Leu250Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000488 in 1,208,949 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 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 0.00012 (0 hom., 4 hem., cov: 24)
  • Exomes 𝑓: 0.000041 (0 hom. 17 hem.)
• Consequence: SLC35A2 NM_005660.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.764
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant X-48905159-G-C is Benign according to our data. Variant chrX-48905159-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 541107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.764 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 4 XL,Unknown gene

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.750C>G	p.Leu250Leu	synonymous	Exon 4 of 5	NP_005651.1
	SLC35A2	NM_001282651.2		c.834C>G	p.Leu278Leu	synonymous	Exon 5 of 5	NP_001269580.1
	SLC35A2	NM_001282650.2		c.789C>G	p.Leu263Leu	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.750C>G	p.Leu250Leu	synonymous	Exon 4 of 5	ENSP00000247138.5
	SLC35A2	ENST00000376521.6	TSL:1	c.750C>G	p.Leu250Leu	synonymous	Exon 4 of 4	ENSP00000365704.1
	SLC35A2	ENST00000445167.7	TSL:1	c.427-267C>G		intron	N/A	ENSP00000402726.2

Frequencies

GnomAD3 genomes AF: 0.000124 AC: 14 AN: 112678 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000840

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: 0.0000938

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000798 AC: 14 AN: 175483 AF XY: 0.0000649

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000185

Gnomad ASJ exome AF: 0.000273

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000775

Gnomad OTH exome AF: 0.000230

GnomAD4 exome AF: 0.0000411 AC: 45 AN: 1096216 Hom.: 0 Cov.: 31 AF XY: 0.0000470 AC XY: 17 AN XY: 361850

African (AFR) AF: 0.00 AC: 0 AN: 26352

American (AMR) AF: 0.000142 AC: 5 AN: 35095

Ashkenazi Jewish (ASJ) AF: 0.000103 AC: 2 AN: 19350

East Asian (EAS) AF: 0.00 AC: 0 AN: 30148

South Asian (SAS) AF: 0.00 AC: 0 AN: 53831

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40121

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4130

European-Non Finnish (NFE) AF: 0.0000380 AC: 32 AN: 841202

Other (OTH) AF: 0.000109 AC: 5 AN: 45987

GnomAD4 genome AF: 0.000124 AC: 14 AN: 112733 Hom.: 0 Cov.: 24 AF XY: 0.000115 AC XY: 4 AN XY: 34877

African (AFR) AF: 0.00 AC: 0 AN: 31082

American (AMR) AF: 0.000839 AC: 9 AN: 10731

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3585

South Asian (SAS) AF: 0.00 AC: 0 AN: 2778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000939 AC: 5 AN: 53274

Other (OTH) AF: 0.00 AC: 0 AN: 1534

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000215

ClinVar

ClinVar submissions as Germline

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	-0.65
CADD	Benign	6.5
DANN	Benign	0.77
PhyloP100		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs375311728; hg19: chrX-48762436; COSMIC: COSV54430869; COSMIC: COSV54430869;