rs188487746

Variant names:

• chrX-111681212-C-G
• rs188487746
• NM_001099922.3:c.-7C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-111681212-C-G
• chrX-111681212-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001099922.3(ALG13):​c.-7C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,096,898 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000036 (0 hom. 2 hem.)
• Consequence: ALG13 NM_001099922.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• 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, 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00000365 (4/1096898) while in subpopulation MID AF = 0.000484 (2/4135). AF 95% confidence interval is 0.0000852. There are 0 homozygotes in GnomAdExome4. There are 2 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	NM_001099922.3	MANE Select	c.-7C>G		5_prime_UTR	Exon 1 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.-307C>G		5_prime_UTR	Exon 1 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.-7C>G		5_prime_UTR	Exon 1 of 26	NP_001311221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	ENST00000394780.8	TSL:2 MANE Select	c.-7C>G		5_prime_UTR	Exon 1 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000371979.7	TSL:1	c.-7C>G		5_prime_UTR	Exon 1 of 4	ENSP00000361047.3	Q9NP73-2
	ALG13	ENST00000927365.1		c.-7C>G		5_prime_UTR	Exon 1 of 27	ENSP00000597424.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1096898 Hom.: 0 Cov.: 30 AF XY: 0.00000552 AC XY: 2 AN XY: 362300

African (AFR) AF: 0.00 AC: 0 AN: 26378

American (AMR) AF: 0.00 AC: 0 AN: 35189

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19373

East Asian (EAS) AF: 0.00 AC: 0 AN: 30189

South Asian (SAS) AF: 0.00 AC: 0 AN: 54088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40513

Middle Eastern (MID) AF: 0.000484 AC: 2 AN: 4135

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 840982

Other (OTH) AF: 0.00 AC: 0 AN: 46051

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.2
DANN	Benign	0.77
PhyloP100		1.1
PromoterAI		-0.078	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs188487746; hg19: chrX-110924440;