chrX-48904604-G-T

Variant names:

• chrX-48904604-G-T
• ENST00000445167.7:c.715C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001032289.3(SLC35A2):​c.715C>A​(p.Leu239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: SLC35A2 NM_001032289.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04
• 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, Labcorp Genetics (formerly Invitae), G2P, Illumina, Orphanet
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13296366).

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+142C>A		intron	N/A	NP_005651.1	P78381-1
	SLC35A2	NM_001032289.3		c.715C>A	p.Leu239Ile	missense	Exon 4 of 4	NP_001027460.1	P78381-3
	SLC35A2	NM_001282648.2		c.643C>A	p.Leu215Ile	missense	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.715C>A	p.Leu239Ile	missense	Exon 4 of 4	ENSP00000402726.2	P78381-3
	SLC35A2	ENST00000376521.6	TSL:1	c.*123C>A		3_prime_UTR	Exon 4 of 4	ENSP00000365704.1	P78381-2
	SLC35A2	ENST00000247138.11	TSL:1 MANE Select	c.1163+142C>A		intron	N/A	ENSP00000247138.5	P78381-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1089844 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 357162

African (AFR) AF: 0.00 AC: 0 AN: 26151

American (AMR) AF: 0.00 AC: 0 AN: 34430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19204

East Asian (EAS) AF: 0.00 AC: 0 AN: 29737

South Asian (SAS) AF: 0.00 AC: 0 AN: 52540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39895

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 837968

Other (OTH) AF: 0.00 AC: 0 AN: 45793

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Benign	0.91
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.0
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.49	T
Polyphen		0.93	P
Vest4		0.20
MutPred		0.15		Gain of sheet (P = 0.0477)
MVP		0.043
ClinPred		0.25	T
GERP RS		3.1
Mutation Taster		=97/3	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

hg19: chrX-48761881;