chrX-111708046-C-G

Variant names:

• chrX-111708046-C-G
• rs1602635058
• NM_001099922.3:c.403C>G

Variant summary

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

The NM_001099922.3(ALG13):​c.403C>G​(p.Gln135Glu) 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. 14/20 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)
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.484
• Publications: 0 publications found

Genes affected

ALG13 (HGNC:30881): (ALG13 UDP-N-acetylglucosaminyltransferase subunit) The protein encoded by this gene is a subunit of a bipartite UDP-N-acetylglucosamine transferase. It heterodimerizes with asparagine-linked glycosylation 14 homolog to form a functional UDP-GlcNAc glycosyltransferase that catalyzes the second sugar addition of the highly conserved oligosaccharide precursor in endoplasmic reticulum N-linked glycosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

ALG13-AS1 (HGNC:41277): (ALG13 antisense RNA 1)

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=0.07638797).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099922.3. 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
	ALG13	NM_001099922.3	MANE Select	c.403C>G	p.Gln135Glu	missense	Exon 4 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.169C>G	p.Gln57Glu	missense	Exon 4 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.403C>G	p.Gln135Glu	missense	Exon 4 of 26	NP_001311221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	ENST00000394780.8	TSL:2 MANE Select	c.403C>G	p.Gln135Glu	missense	Exon 4 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.403C>G	p.Gln135Glu	missense	Exon 4 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.403C>G	p.Gln135Glu	missense	Exon 4 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy, 36 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.8
DANN	Benign	0.92
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.48
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.034
Sift	Benign	0.064	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.074
MutPred		0.50		Gain of ubiquitination at K137 (P = 0.0314)
MVP		0.42
MPC		0.22
ClinPred		0.036	T
GERP RS		0.67
Varity_R		0.075
gMVP		0.39
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1602635058; hg19: chrX-110951274;