rs1556516959

Variant names:

• chrX-111736771-G-T
• rs1556516959
• NM_001099922.3:c.2587G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099922.3(ALG13):​c.2587G>T​(p.Val863Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 4.90
• 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, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37070006).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	NM_001099922.3	MANE Select	c.2587G>T	p.Val863Phe	missense	Exon 23 of 27	NP_001093392.1
	ALG13	NM_001257231.2		c.2353G>T	p.Val785Phe	missense	Exon 23 of 27	NP_001244160.1
	ALG13	NM_001324292.2		c.2587G>T	p.Val863Phe	missense	Exon 23 of 26	NP_001311221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	ENST00000394780.8	TSL:2 MANE Select	c.2587G>T	p.Val863Phe	missense	Exon 23 of 27	ENSP00000378260.3
	ALG13	ENST00000623622.2	TSL:5	c.2413G>T	p.Val805Phe	missense	Exon 21 of 24	ENSP00000485624.2
	ALG13	ENST00000436609.5	TSL:5	c.2275G>T	p.Val759Phe	missense	Exon 23 of 26	ENSP00000392990.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Developmental and epileptic encephalopathy, 36 Uncertain:1

Sep 01, 2021

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.9
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.081	T
Polyphen		0.77	P
Vest4		0.27
MutPred		0.25		Loss of disorder (P = 0.1261)
MVP		0.72
MPC		0.59
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.54
gMVP		0.39
Mutation Taster		=84/16	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1556516959; hg19: chrX-110979999;