rs760819207

Variant names:

• chrX-111759826-G-A
• rs760819207
• NM_001099922.3:c.3241G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099922.3(ALG13):​c.3241G>A​(p.Gly1081Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000273 in 1,097,614 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1081D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.31
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23125625).

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.3241G>A	p.Gly1081Ser	missense	Exon 27 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.3007G>A	p.Gly1003Ser	missense	Exon 27 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.3004G>A	p.Gly1002Ser	missense	Exon 26 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.3241G>A	p.Gly1081Ser	missense	Exon 27 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.3217G>A	p.Gly1073Ser	missense	Exon 27 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.3067G>A	p.Gly1023Ser	missense	Exon 25 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00000563 AC: 1 AN: 177764 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000227

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097614 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363182

African (AFR) AF: 0.00 AC: 0 AN: 26393

American (AMR) AF: 0.0000854 AC: 3 AN: 35115

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19377

East Asian (EAS) AF: 0.00 AC: 0 AN: 30155

South Asian (SAS) AF: 0.00 AC: 0 AN: 54046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40481

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841849

Other (OTH) AF: 0.00 AC: 0 AN: 46062

GnomAD4 genome Cov.: 22

ExAC AF: 0.00000831 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy, 36 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.16
Sift	Uncertain	0.010	D
Sift4G	Benign	0.17	T
Polyphen		0.58	P
Vest4		0.19
MutPred		0.21		Loss of relative solvent accessibility (P = 0.0071)
MVP		0.73
MPC		0.21
ClinPred		0.48	T
GERP RS		4.9
PromoterAI		-0.010	Neutral
Varity_R		0.15
gMVP		0.54
Mutation Taster		=92/8	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs760819207; hg19: chrX-111003054;