NM_005660.3:c.236G>T

Variant names:

• chrX-48909852-C-A
• rs1057524438
• NM_005660.3:c.236G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005660.3(SLC35A2):​c.236G>T​(p.Gly79Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000073 in 1,096,013 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. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000073 (0 hom. 0 hem.)
• Consequence: SLC35A2 NM_005660.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.72
• Publications: 3 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.113).

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.236G>T	p.Gly79Val	missense	Exon 2 of 5	NP_005651.1
	SLC35A2	NM_001282651.2		c.320G>T	p.Gly107Val	missense	Exon 3 of 5	NP_001269580.1
	SLC35A2	NM_001282650.2		c.275G>T	p.Gly92Val	missense	Exon 2 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.236G>T	p.Gly79Val	missense	Exon 2 of 5	ENSP00000247138.5
	SLC35A2	ENST00000376521.6	TSL:1	c.236G>T	p.Gly79Val	missense	Exon 2 of 4	ENSP00000365704.1
	SLC35A2	ENST00000445167.7	TSL:1	c.236G>T	p.Gly79Val	missense	Exon 2 of 4	ENSP00000402726.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000730 AC: 8 AN: 1096013 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 361517

African (AFR) AF: 0.00 AC: 0 AN: 26383

American (AMR) AF: 0.00 AC: 0 AN: 34978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19309

East Asian (EAS) AF: 0.00 AC: 0 AN: 30161

South Asian (SAS) AF: 0.00 AC: 0 AN: 53526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40385

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4123

European-Non Finnish (NFE) AF: 0.00000951 AC: 8 AN: 841123

Other (OTH) AF: 0.00 AC: 0 AN: 46025

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	SLC35A2-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Benign	0.94
FATHMM_MKL	Benign	0.43	N
M_CAP	Uncertain	0.19	D
PhyloP100		5.7
ClinPred		0.80	D
GERP RS		5.0
PromoterAI		-0.041	Neutral
Varity_R		0.32
Mutation Taster		=71/29	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: rs1057524438; hg19: chrX-48767129;