chrX-111736835-C-A

Variant names:

• chrX-111736835-C-A
• rs1556517111
• NM_001099922.3:c.2651C>A

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.2651C>A​(p.Ala884Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A884V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• 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 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 36

  Inheritance: XL Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

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=0.24790421).

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.2651C>A	p.Ala884Asp	missense	Exon 23 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.2417C>A	p.Ala806Asp	missense	Exon 23 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.2651C>A	p.Ala884Asp	missense	Exon 23 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.2651C>A	p.Ala884Asp	missense	Exon 23 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.2627C>A	p.Ala876Asp	missense	Exon 23 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.2477C>A	p.Ala826Asp	missense	Exon 21 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	D
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.60	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.1
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.050	T
Polyphen		0.88	P
Vest4		0.34
MutPred		0.24		Loss of helix (P = 0.079)
MVP		0.75
MPC		0.53
ClinPred		0.94	D
GERP RS		4.4
Varity_R		0.60
gMVP		0.33
Mutation Taster		=91/9	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1556517111; hg19: chrX-110980063;