X-48909986-G-A

Variant names:

• chrX-48909986-G-A
• rs977233420
• NM_005660.3:c.102C>T

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.102C>T​(p.Arg34Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,206,637 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 0.0000089 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000016 (0 hom. 3 hem.)
• Consequence: SLC35A2 NM_005660.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.48
• 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=-0.48).
• BP6: Variant X-48909986-G-A is Benign according to our data. Variant chrX-48909986-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 474045.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.48 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 3 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A2	NM_005660.3	c.102C>T	p.Arg34Arg	synonymous_variant	Exon 2 of 5	ENST00000247138.11	NP_005651.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A2	ENST00000247138.11	c.102C>T	p.Arg34Arg	synonymous_variant	Exon 2 of 5	1	NM_005660.3	ENSP00000247138.5

Frequencies

GnomAD3 genomes AF: 0.00000891 AC: 1 AN: 112284 Hom.: 0 Cov.: 24

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000573 AC: 1 AN: 174623 AF XY: 0.00

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: 0.0000129

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 18 AN: 1094353 Hom.: 0 Cov.: 30 AF XY: 0.00000833 AC XY: 3 AN XY: 360119

African (AFR) AF: 0.00 AC: 0 AN: 26357

American (AMR) AF: 0.00 AC: 0 AN: 34899

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19176

East Asian (EAS) AF: 0.00 AC: 0 AN: 30129

South Asian (SAS) AF: 0.00 AC: 0 AN: 53288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4059

European-Non Finnish (NFE) AF: 0.0000202 AC: 17 AN: 840179

Other (OTH) AF: 0.0000218 AC: 1 AN: 45948

GnomAD4 genome AF: 0.00000891 AC: 1 AN: 112284 Hom.: 0 Cov.: 24 AF XY: 0.0000290 AC XY: 1 AN XY: 34438

African (AFR) AF: 0.00 AC: 0 AN: 30869

American (AMR) AF: 0.00 AC: 0 AN: 10637

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3598

South Asian (SAS) AF: 0.00 AC: 0 AN: 2746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6171

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

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53171

Other (OTH) AF: 0.00 AC: 0 AN: 1514

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLC35A2-congenital disorder of glycosylation Benign:1

Oct 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		2.5
PromoterAI		0.00060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs977233420; hg19: chrX-48767263;