rs1556516959

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3	c.2587G>T	p.Val863Phe	missense_variant	Exon 23 of 27	ENST00000394780.8	NP_001093392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8	c.2587G>T	p.Val863Phe	missense_variant	Exon 23 of 27	2	NM_001099922.3	ENSP00000378260.3

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

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Computational scores

Source: dbNSFP v4.3

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;T;.;T;.
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.2	M;.;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.2	D;.;D;.;.
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D;.;D;.;.
Sift4G	Benign	0.081	T;T;D;D;D
Polyphen		0.77	P;P;P;P;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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556516959; hg19: chrX-110979999;