rs1064796719

Variant names:

• chrX-111757744-G-A
• rs1064796719
• NM_001099922.3:c.3130G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001099922.3(ALG13):​c.3130G>A​(p.Ala1044Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000913 in 1,205,081 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. A1044V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.0000064 (0 hom. 2 hem.)
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 0.583
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040436715).
• 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.3130G>A	p.Ala1044Thr	missense	Exon 26 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.2896G>A	p.Ala966Thr	missense	Exon 26 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.2893G>A	p.Ala965Thr	missense	Exon 25 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.3130G>A	p.Ala1044Thr	missense	Exon 26 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.3106G>A	p.Ala1036Thr	missense	Exon 26 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.2956G>A	p.Ala986Thr	missense	Exon 24 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes AF: 0.0000360 AC: 4 AN: 111260 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000565

Gnomad OTH AF: 0.000670

GnomAD4 exome AF: 0.00000640 AC: 7 AN: 1093821 Hom.: 0 Cov.: 30 AF XY: 0.00000556 AC XY: 2 AN XY: 359715

African (AFR) AF: 0.00 AC: 0 AN: 26195

American (AMR) AF: 0.00 AC: 0 AN: 34310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19131

East Asian (EAS) AF: 0.00 AC: 0 AN: 30129

South Asian (SAS) AF: 0.00 AC: 0 AN: 52919

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40465

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4079

European-Non Finnish (NFE) AF: 0.00000833 AC: 7 AN: 840676

Other (OTH) AF: 0.00 AC: 0 AN: 45917

GnomAD4 genome AF: 0.0000360 AC: 4 AN: 111260 Hom.: 0 Cov.: 22 AF XY: 0.0000299 AC XY: 1 AN XY: 33454

African (AFR) AF: 0.00 AC: 0 AN: 30597

American (AMR) AF: 0.00 AC: 0 AN: 10386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3538

South Asian (SAS) AF: 0.00 AC: 0 AN: 2640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53085

Other (OTH) AF: 0.000670 AC: 1 AN: 1492

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Developmental and epileptic encephalopathy, 36 (2)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.8
DANN	Benign	0.45
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.58
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.055
Sift	Benign	0.081	T
Sift4G	Benign	0.27	T
Polyphen		0.0050	B
Vest4		0.038
MutPred		0.16		Loss of sheet (P = 0.0817)
MVP		0.30
MPC		0.17
ClinPred		0.032	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.095
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1064796719; hg19: chrX-111000972;