NM_001099922.3:c.1591T>C

Variant names:

• chrX-111723888-T-C
• rs112837367
• NM_001099922.3:c.1591T>C

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.1591T>C​(p.Leu531Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,141,864 control chromosomes in the GnomAD database, including 1 homozygotes. There are 60 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 0.00085 (0 hom., 23 hem., cov: 23)
  • Exomes 𝑓: 0.00013 (1 hom. 37 hem.)
• Consequence: ALG13 NM_001099922.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.650
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-111723888-T-C is Benign according to our data. Variant chrX-111723888-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 387963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.65 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000848 (95/111992) while in subpopulation AFR AF = 0.00275 (85/30896). AF 95% confidence interval is 0.00228. There are 0 homozygotes in GnomAd4. There are 23 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 23 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.1591T>C	p.Leu531Leu	synonymous	Exon 14 of 27	NP_001093392.1
	ALG13	NM_001257231.2		c.1357T>C	p.Leu453Leu	synonymous	Exon 14 of 27	NP_001244160.1
	ALG13	NM_001324292.2		c.1591T>C	p.Leu531Leu	synonymous	Exon 14 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.1591T>C	p.Leu531Leu	synonymous	Exon 14 of 27	ENSP00000378260.3
	ALG13	ENST00000927365.1		c.1591T>C	p.Leu531Leu	synonymous	Exon 14 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.1417T>C	p.Leu473Leu	synonymous	Exon 12 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes AF: 0.000849 AC: 95 AN: 111937 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00276

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000570

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00844

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.000670

GnomAD2 exomes AF: 0.000350 AC: 44 AN: 125641 AF XY: 0.000333

Gnomad AFR exome AF: 0.00328

Gnomad AMR exome AF: 0.000642

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000105

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000320

GnomAD4 exome AF: 0.000134 AC: 138 AN: 1029872 Hom.: 1 Cov.: 20 AF XY: 0.000120 AC XY: 37 AN XY: 309488

African (AFR) AF: 0.00286 AC: 70 AN: 24455

American (AMR) AF: 0.000657 AC: 18 AN: 27395

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17999

East Asian (EAS) AF: 0.0000347 AC: 1 AN: 28850

South Asian (SAS) AF: 0.000194 AC: 9 AN: 46444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39371

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3509

European-Non Finnish (NFE) AF: 0.0000288 AC: 23 AN: 798238

Other (OTH) AF: 0.000390 AC: 17 AN: 43611

GnomAD4 genome AF: 0.000848 AC: 95 AN: 111992 Hom.: 0 Cov.: 23 AF XY: 0.000674 AC XY: 23 AN XY: 34146

African (AFR) AF: 0.00275 AC: 85 AN: 30896

American (AMR) AF: 0.000569 AC: 6 AN: 10543

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3546

South Asian (SAS) AF: 0.00 AC: 0 AN: 2663

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6034

Middle Eastern (MID) AF: 0.00922 AC: 2 AN: 217

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53245

Other (OTH) AF: 0.000661 AC: 1 AN: 1512

Alfa AF: 0.000783 Hom.: 2

Bravo AF: 0.00128

ClinVar

ClinVar submissions as Germline

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	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.096
DANN	Benign	0.44
PhyloP100		-0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs112837367; hg19: chrX-110967116;