rs782316882

Variant names:

• chrX-48904691-TC-T
• rs782316882
• ENST00000445167.7:c.627delG

Your query was ambiguous. Multiple possible variants found:

• chrX-48904691-TC-T
• chrX-48904691-TC-TCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PVS1_Strong BS2

The NM_001032289.3(SLC35A2):​c.627delG​(p.Thr210LeufsTer42) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,206,652 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 47 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000054 (0 hom., 2 hem., cov: 23)
  • Exomes 𝑓: 0.00011 (0 hom. 45 hem.)
• Consequence: SLC35A2 NM_001032289.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.600
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.14 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• BS2: High Hemizygotes in GnomAd4 at 2 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032289.3. 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.1163+54delG		intron	N/A	NP_005651.1	P78381-1
	SLC35A2	NM_001032289.3		c.627delG	p.Thr210LeufsTer42	frameshift	Exon 4 of 4	NP_001027460.1	P78381-3
	SLC35A2	NM_001282648.2		c.555delG	p.Thr186LeufsTer42	frameshift	Exon 4 of 4	NP_001269577.1	A6NKM8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A2	ENST00000445167.7	TSL:1	c.627delG	p.Thr210LeufsTer42	frameshift	Exon 4 of 4	ENSP00000402726.2	P78381-3
	SLC35A2	ENST00000376521.6	TSL:1	c.*35delG		3_prime_UTR	Exon 4 of 4	ENSP00000365704.1	P78381-2
	SLC35A2	ENST00000247138.11	TSL:1 MANE Select	c.1163+54delG		intron	N/A	ENSP00000247138.5	P78381-1

Frequencies

GnomAD3 genomes AF: 0.0000542 AC: 6 AN: 110746 Hom.: 0 Cov.: 23

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: 0.000114

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 179919 AF XY: 0.0000154

Gnomad AFR exome AF: 0.00

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: 0.0000250

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000110 AC: 121 AN: 1095906 Hom.: 0 Cov.: 31 AF XY: 0.000125 AC XY: 45 AN XY: 361382

African (AFR) AF: 0.00 AC: 0 AN: 26369

American (AMR) AF: 0.00 AC: 0 AN: 35151

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19310

East Asian (EAS) AF: 0.00 AC: 0 AN: 30189

South Asian (SAS) AF: 0.00 AC: 0 AN: 53882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40459

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4117

European-Non Finnish (NFE) AF: 0.000138 AC: 116 AN: 840406

Other (OTH) AF: 0.000109 AC: 5 AN: 46023

GnomAD4 genome AF: 0.0000542 AC: 6 AN: 110746 Hom.: 0 Cov.: 23 AF XY: 0.0000604 AC XY: 2 AN XY: 33134

African (AFR) AF: 0.00 AC: 0 AN: 30406

American (AMR) AF: 0.00 AC: 0 AN: 10501

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2627

East Asian (EAS) AF: 0.00 AC: 0 AN: 3520

South Asian (SAS) AF: 0.00 AC: 0 AN: 2621

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5995

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000114 AC: 6 AN: 52687

Other (OTH) AF: 0.00 AC: 0 AN: 1479

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.60
Mutation Taster		=163/37	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: rs782316882; hg19: chrX-48761968;