rs139631003

Variant names:

• chrX-111686132-A-G
• rs139631003
• NM_001099922.3:c.383+1029A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001168385.3(ALG13):​c.384-5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,116,505 control chromosomes in the GnomAD database, including 5 homozygotes. There are 331 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (4 hom., 174 hem., cov: 23)
  • Exomes 𝑓: 0.00061 (1 hom. 157 hem.)
• Consequence: ALG13 NM_001168385.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001616
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.51
• Publications: 1 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant X-111686132-A-G is Benign according to our data. Variant chrX-111686132-A-G is described in ClinVar as Benign. ClinVar VariationId is 382136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00581 (653/112378) while in subpopulation AFR AF = 0.0198 (614/30960). AF 95% confidence interval is 0.0185. There are 4 homozygotes in GnomAd4. There are 174 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168385.3. 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.383+1029A>G		intron	N/A	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.149+1029A>G		intron	N/A	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.383+1029A>G		intron	N/A	NP_001311221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	ENST00000394780.8	TSL:2 MANE Select	c.383+1029A>G		intron	N/A	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000371979.7	TSL:1	c.383+1029A>G		intron	N/A	ENSP00000361047.3	Q9NP73-2
	ALG13	ENST00000927365.1		c.383+1029A>G		intron	N/A	ENSP00000597424.1

Frequencies

GnomAD3 genomes AF: 0.00575 AC: 646 AN: 112336 Hom.: 4 Cov.: 23

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00273

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.00132

GnomAD2 exomes AF: 0.00134 AC: 102 AN: 75955 AF XY: 0.000543

Gnomad AFR exome AF: 0.0167

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000185

Gnomad FIN exome AF: 0.000280

Gnomad NFE exome AF: 0.0000922

Gnomad OTH exome AF: 0.000886

GnomAD4 exome AF: 0.000606 AC: 609 AN: 1004127 Hom.: 1 Cov.: 21 AF XY: 0.000500 AC XY: 157 AN XY: 313987

African (AFR) AF: 0.0187 AC: 440 AN: 23530

American (AMR) AF: 0.00153 AC: 36 AN: 23471

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17542

East Asian (EAS) AF: 0.00 AC: 0 AN: 25782

South Asian (SAS) AF: 0.00 AC: 0 AN: 42948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25897

Middle Eastern (MID) AF: 0.000774 AC: 3 AN: 3875

European-Non Finnish (NFE) AF: 0.000108 AC: 86 AN: 798497

Other (OTH) AF: 0.00103 AC: 44 AN: 42585

GnomAD4 genome AF: 0.00581 AC: 653 AN: 112378 Hom.: 4 Cov.: 23 AF XY: 0.00504 AC XY: 174 AN XY: 34552

African (AFR) AF: 0.0198 AC: 614 AN: 30960

American (AMR) AF: 0.00272 AC: 29 AN: 10649

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3580

South Asian (SAS) AF: 0.00 AC: 0 AN: 2752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6091

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000150 AC: 8 AN: 53253

Other (OTH) AF: 0.00130 AC: 2 AN: 1537

Alfa AF: 0.00326 Hom.: 14

Bravo AF: 0.00638

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Developmental and epileptic encephalopathy, 36 (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.033
DANN	Benign	0.56
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0080
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs139631003; hg19: chrX-110929360;