NM_005660.3:c.30C>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005660.3(SLC35A2):​c.30C>A​(p.Thr10Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000172 in 1,163,444 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T10T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
• Consequence: SLC35A2 NM_005660.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.409 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.30C>A	p.Thr10Thr	synonymous	Exon 1 of 5	NP_005651.1	P78381-1
	SLC35A2	NM_001282651.2		c.30C>A	p.Thr10Thr	synonymous	Exon 1 of 5	NP_001269580.1	P78381-4
	SLC35A2	NM_001282650.2		c.30C>A	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>A	p.Thr10Thr	synonymous	Exon 1 of 5	ENSP00000247138.5	P78381-1
	SLC35A2	ENST00000376521.6	TSL:1	c.30C>A	p.Thr10Thr	synonymous	Exon 1 of 4	ENSP00000365704.1	P78381-2
	SLC35A2	ENST00000445167.7	TSL:1	c.30C>A	p.Thr10Thr	synonymous	Exon 1 of 4	ENSP00000402726.2	P78381-3

Frequencies

GnomAD3 genomes AF: 0.00000883 AC: 1 AN: 113311 Hom.: 0 Cov.: 25

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: 0.0000187

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.52e-7 AC: 1 AN: 1050133 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 342779

African (AFR) AF: 0.0000400 AC: 1 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: 0.00 AC: 0 AN: 31162

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 821310

Other (OTH) AF: 0.00 AC: 0 AN: 44358

GnomAD4 genome AF: 0.00000883 AC: 1 AN: 113311 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 35447

African (AFR) AF: 0.00 AC: 0 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: 0.0000187 AC: 1 AN: 53341

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.3
DANN	Benign	0.84
PhyloP100		0.41
PromoterAI		-0.069	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;