rs778396216

Variant names:

• chrX-111730526-G-A
• rs778396216
• NM_001099922.3:c.2403G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-111730526-G-A
• chrX-111730526-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001099922.3(ALG13):​c.2403G>A​(p.Glu801Glu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000925 in 1,080,901 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: ALG13 NM_001099922.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.00006907
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• 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, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.256 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	NM_001099922.3	MANE Select	c.2403G>A	p.Glu801Glu	splice_region synonymous	Exon 21 of 27	NP_001093392.1
	ALG13	NM_001257231.2		c.2169G>A	p.Glu723Glu	splice_region synonymous	Exon 21 of 27	NP_001244160.1
	ALG13	NM_001324292.2		c.2403G>A	p.Glu801Glu	splice_region synonymous	Exon 21 of 26	NP_001311221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	ENST00000394780.8	TSL:2 MANE Select	c.2403G>A	p.Glu801Glu	splice_region synonymous	Exon 21 of 27	ENSP00000378260.3
	ALG13	ENST00000623622.2	TSL:5	c.2229G>A	p.Glu743Glu	splice_region synonymous	Exon 19 of 24	ENSP00000485624.2
	ALG13	ENST00000436609.5	TSL:5	c.2091G>A	p.Glu697Glu	splice_region synonymous	Exon 21 of 26	ENSP00000392990.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.25e-7 AC: 1 AN: 1080901 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 351147

African (AFR) AF: 0.00 AC: 0 AN: 26145

American (AMR) AF: 0.00 AC: 0 AN: 32940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19040

East Asian (EAS) AF: 0.00 AC: 0 AN: 29793

South Asian (SAS) AF: 0.00 AC: 0 AN: 51808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3746

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 832330

Other (OTH) AF: 0.00 AC: 0 AN: 45437

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.3
DANN	Benign	0.71
PhyloP100		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000069
dbscSNV1_RF	Benign	0.060

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

Other links and lift over

dbSNP: rs778396216; hg19: chrX-110973754;