X-48911607-G-C

Variant names:

• chrX-48911607-G-C
• rs373480204
• NM_005660.3:c.30C>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005660.3(SLC35A2):​c.30C>G​(p.Thr10Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,163,447 control chromosomes in the GnomAD database, including 1 homozygotes. There are 176 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T10T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., 9 hem., cov: 25)
  • Exomes 𝑓: 0.00047 (1 hom. 167 hem.)
• Consequence: SLC35A2 NM_005660.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.409
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant X-48911607-G-C is Benign according to our data. Variant chrX-48911607-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 474047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.409 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 9 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A2	NM_005660.3	MANE Select	c.30C>G	p.Thr10Thr	synonymous	Exon 1 of 5	NP_005651.1	P78381-1
	SLC35A2	NM_001282651.2		c.30C>G	p.Thr10Thr	synonymous	Exon 1 of 5	NP_001269580.1	P78381-4
	SLC35A2	NM_001282650.2		c.30C>G	p.Thr10Thr	synonymous	Exon 1 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.30C>G	p.Thr10Thr	synonymous	Exon 1 of 5	ENSP00000247138.5	P78381-1
	SLC35A2	ENST00000376521.6	TSL:1	c.30C>G	p.Thr10Thr	synonymous	Exon 1 of 4	ENSP00000365704.1	P78381-2
	SLC35A2	ENST00000445167.7	TSL:1	c.30C>G	p.Thr10Thr	synonymous	Exon 1 of 4	ENSP00000402726.2	P78381-3

Frequencies

GnomAD3 genomes AF: 0.000371 AC: 42 AN: 113311 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000128

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: 0.000712

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000225 AC: 24 AN: 106777 AF XY: 0.000162

Gnomad AFR exome AF: 0.000164

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: 0.000523

Gnomad OTH exome AF: 0.000314

GnomAD4 exome AF: 0.000469 AC: 492 AN: 1050136 Hom.: 1 Cov.: 31 AF XY: 0.000487 AC XY: 167 AN XY: 342782

African (AFR) AF: 0.0000800 AC: 2 AN: 24991

American (AMR) AF: 0.00 AC: 0 AN: 28765

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18652

East Asian (EAS) AF: 0.00 AC: 0 AN: 27354

South Asian (SAS) AF: 0.00 AC: 0 AN: 50027

European-Finnish (FIN) AF: 0.000225 AC: 7 AN: 31164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3514

European-Non Finnish (NFE) AF: 0.000573 AC: 471 AN: 821311

Other (OTH) AF: 0.000271 AC: 12 AN: 44358

GnomAD4 genome AF: 0.000371 AC: 42 AN: 113311 Hom.: 0 Cov.: 25 AF XY: 0.000254 AC XY: 9 AN XY: 35447

African (AFR) AF: 0.000128 AC: 4 AN: 31278

American (AMR) AF: 0.00 AC: 0 AN: 10841

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3603

South Asian (SAS) AF: 0.00 AC: 0 AN: 2833

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6309

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.000712 AC: 38 AN: 53341

Other (OTH) AF: 0.00 AC: 0 AN: 1529

Alfa AF: 0.000218 Hom.: 2

Bravo AF: 0.000268

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)
-	-	1	SLC35A2-congenital disorder of glycosylation (1)
-	-	1	SLC35A2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.5
DANN	Benign	0.78
PhyloP100		0.41
PromoterAI		-0.0020	Neutral
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: rs373480204; hg19: chrX-48768884;