NM_001099922.3:c.3039A>G

Variant names:

• chrX-111757653-A-G
• rs183032531
• NM_001099922.3:c.3039A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001099922.3(ALG13):​c.3039A>G​(p.Val1013Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000635 in 1,207,045 control chromosomes in the GnomAD database, including 5 homozygotes. There are 208 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., 117 hem., cov: 22)
  • Exomes 𝑓: 0.00032 (2 hom. 91 hem.)
• Consequence: ALG13 NM_001099922.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0330
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-111757653-A-G is Benign according to our data. Variant chrX-111757653-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 383513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.033 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0037 (410/110938) while in subpopulation AFR AF = 0.0128 (391/30526). AF 95% confidence interval is 0.0118. There are 3 homozygotes in GnomAd4. There are 117 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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.3039A>G	p.Val1013Val	synonymous	Exon 26 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.2805A>G	p.Val935Val	synonymous	Exon 26 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.2802A>G	p.Val934Val	synonymous	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.3039A>G	p.Val1013Val	synonymous	Exon 26 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.3015A>G	p.Val1005Val	synonymous	Exon 26 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.2865A>G	p.Val955Val	synonymous	Exon 24 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 401 AN: 110888 Hom.: 3 Cov.: 22

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000777

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000384

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000943

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.000953 AC: 169 AN: 177262 AF XY: 0.000598

Gnomad AFR exome AF: 0.0131

Gnomad AMR exome AF: 0.000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000128

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000325 AC: 356 AN: 1096107 Hom.: 2 Cov.: 30 AF XY: 0.000252 AC XY: 91 AN XY: 361697

African (AFR) AF: 0.0113 AC: 298 AN: 26325

American (AMR) AF: 0.000370 AC: 13 AN: 35097

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19356

East Asian (EAS) AF: 0.00 AC: 0 AN: 30142

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 53938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40499

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.00000952 AC: 8 AN: 840607

Other (OTH) AF: 0.000782 AC: 36 AN: 46016

GnomAD4 genome AF: 0.00370 AC: 410 AN: 110938 Hom.: 3 Cov.: 22 AF XY: 0.00353 AC XY: 117 AN XY: 33172

African (AFR) AF: 0.0128 AC: 391 AN: 30526

American (AMR) AF: 0.000776 AC: 8 AN: 10303

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3520

South Asian (SAS) AF: 0.000385 AC: 1 AN: 2597

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5949

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

European-Non Finnish (NFE) AF: 0.0000943 AC: 5 AN: 52995

Other (OTH) AF: 0.00332 AC: 5 AN: 1507

Alfa AF: 0.00143 Hom.: 8

Bravo AF: 0.00390

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Developmental and epileptic encephalopathy, 36 (3)
-	-	2	not specified (2)
-	-	1	ALG13-related disorder (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.9
DANN	Benign	0.74
PhyloP100		-0.033
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs183032531; hg19: chrX-111000881;