rs745411126

chrX-111730395-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001099922.3(ALG13):c.2369G>A(p.Gly790Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000082 in 1,207,441 control chromosomes in the GnomAD database, including 1 homozygotes. There are 56 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., 3 hem., cov: 24)
  • Exomes 𝑓: 0.000082 (1 hom. 53 hem.)
• Consequence: ALG13 NM_001099922.3 missense, splice_region
• Scores: Splicing: ADA: 0.1086
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.84

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010570288).
• BP6: Variant X-111730395-G-A is Benign according to our data. Variant chrX-111730395-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 508546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111730395-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000803 (9/112078) while in subpopulation SAS AF= 0.00295 (8/2709). AF 95% confidence interval is 0.00147. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3	c.2369G>A	p.Gly790Glu	missense_variant, splice_region_variant	20/27	ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8	c.2369G>A	p.Gly790Glu	missense_variant, splice_region_variant	20/27	2	NM_001099922.3	A2

Frequencies

GnomAD3 genomes AF: 0.0000803 AC: 9 AN: 112024 Hom.: 0 Cov.: 24 AF XY: 0.0000876 AC XY: 3 AN XY: 34248

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00294

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000192 AC: 34 AN: 176945 Hom.: 0 AF XY: 0.000262 AC XY: 17 AN XY: 64993

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00184

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000822 AC: 90 AN: 1095363 Hom.: 1 Cov.: 29 AF XY: 0.000147 AC XY: 53 AN XY: 361061

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.000131

GnomAD4 genome AF: 0.0000803 AC: 9 AN: 112078 Hom.: 0 Cov.: 24 AF XY: 0.0000874 AC XY: 3 AN XY: 34312

Gnomad4 AFR AF: 0.0000323

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00295

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000227

ExAC AF: 0.000308 AC: 37

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 36 Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 11, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 20, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 20, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;.;.;.;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T;T;.;T;.
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.011	T;T;T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Uncertain	2.2	M;.;.;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.3	D;.;D;.;.
REVEL	Benign	0.24
Sift	Benign	0.043	D;.;D;.;.
Sift4G	Uncertain	0.014	D;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.53
MutPred		0.25		Gain of solvent accessibility (P = 0.005);.;.;.;.;
MVP		0.71
MPC		0.82
ClinPred		0.23	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.40
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.11
dbscSNV1_RF	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs745411126; hg19: chrX-110973623;