X-111681268-T-A

Position:

• chrX-111681268-T-A

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2 PP3_Strong PP5_Moderate

The NM_001099922.3(ALG13):​c.50T>A​(p.Ile17Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:3
• Conservation: PhyloP100: 6.69

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 Likely_pathogenic. Variant got 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958
• PP5: Variant X-111681268-T-A is Pathogenic according to our data. Variant chrX-111681268-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 598969.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3	c.50T>A	p.Ile17Asn	missense_variant	1/27	ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8	c.50T>A	p.Ile17Asn	missense_variant	1/27	2	NM_001099922.3	A2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

Submissions by phenotype

Osteopenia;C0557874:Global developmental delay;C3887898:Infantile spasms;C4048268:Cerebral visual impairment;C4551563:Microcephaly Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Center for Personalized Medicine, Children's Hospital Los Angeles

-

- -

Congenital disorder of glycosylation Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

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- -

See cases Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Center for Personalized Medicine, Children's Hospital Los Angeles

Dec 21, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	.;T;T;.;D
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;D;D;D;T
M_CAP	Pathogenic	0.42	D
MetaRNN	Pathogenic	0.96	D;D;D;D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Pathogenic	3.6	H;H;.;.;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.3	D;N;.;.;.
REVEL	Uncertain	0.61
Sift	Uncertain	0.020	D;D;.;.;.
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		0.48	P;D;.;.;.
Vest4		0.81
MutPred		0.83		Loss of stability (P = 0.0544);Loss of stability (P = 0.0544);Loss of stability (P = 0.0544);Loss of stability (P = 0.0544);.;
MVP		0.81
MPC		0.46
ClinPred		0.98	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.77
gMVP		0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs1569508922; hg19: chrX-110924496;