rs201820102

Variant names:

• chrX-111759999-A-C
• rs201820102
• NM_001099922.3:c.3414A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BS1 BS2

The NM_001099922.3(ALG13):​c.3414A>C​(p.Ter1138Tyrext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.00129 in 1,206,161 control chromosomes in the GnomAD database, including 2 homozygotes. There are 483 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 0.00087 (0 hom., 20 hem., cov: 23)
  • Exomes 𝑓: 0.0013 (2 hom. 463 hem.)
• Consequence: ALG13 NM_001099922.3 stop_lost
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 4.58
• Publications: 5 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 -14 ACMG points.

• PM4: Stoplost variant in NM_001099922.3 Downstream stopcodon found after 1153 codons.
• BP6: Variant X-111759999-A-C is Benign according to our data. Variant chrX-111759999-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 377466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000866 (97/112012) while in subpopulation NFE AF = 0.00152 (81/53243). AF 95% confidence interval is 0.00125. There are 0 homozygotes in GnomAd4. There are 20 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 20 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.3414A>C	p.Ter1138Tyrext*?	stop_lost	Exon 27 of 27	NP_001093392.1
	ALG13	NM_001257231.2		c.3180A>C	p.Ter1060Tyrext*?	stop_lost	Exon 27 of 27	NP_001244160.1
	ALG13	NM_001324292.2		c.3177A>C	p.Ter1059Tyrext*?	stop_lost	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.3414A>C	p.Ter1138Tyrext*?	stop_lost	Exon 27 of 27	ENSP00000378260.3
	ALG13	ENST00000927365.1		c.3390A>C	p.Ter1130Tyrext*?	stop_lost	Exon 27 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.3240A>C	p.Ter1080Tyrext*?	stop_lost	Exon 25 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes AF: 0.000866 AC: 97 AN: 111960 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000374

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00152

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000645 AC: 113 AN: 175314 AF XY: 0.000598

Gnomad AFR exome AF: 0.000245

Gnomad AMR exome AF: 0.000149

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000746

Gnomad FIN exome AF: 0.0000636

Gnomad NFE exome AF: 0.00126

Gnomad OTH exome AF: 0.000691

GnomAD4 exome AF: 0.00133 AC: 1457 AN: 1094149 Hom.: 2 Cov.: 30 AF XY: 0.00129 AC XY: 463 AN XY: 359889

African (AFR) AF: 0.000114 AC: 3 AN: 26325

American (AMR) AF: 0.000115 AC: 4 AN: 34844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19223

East Asian (EAS) AF: 0.0000332 AC: 1 AN: 30114

South Asian (SAS) AF: 0.000262 AC: 14 AN: 53385

European-Finnish (FIN) AF: 0.000347 AC: 14 AN: 40400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4110

European-Non Finnish (NFE) AF: 0.00163 AC: 1370 AN: 839822

Other (OTH) AF: 0.00111 AC: 51 AN: 45926

GnomAD4 genome AF: 0.000866 AC: 97 AN: 112012 Hom.: 0 Cov.: 23 AF XY: 0.000585 AC XY: 20 AN XY: 34174

African (AFR) AF: 0.000356 AC: 11 AN: 30881

American (AMR) AF: 0.000380 AC: 4 AN: 10535

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3571

South Asian (SAS) AF: 0.000375 AC: 1 AN: 2669

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6045

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00152 AC: 81 AN: 53243

Other (OTH) AF: 0.00 AC: 0 AN: 1524

Alfa AF: 0.00117 Hom.: 53

Bravo AF: 0.000737

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00138 AC: 4

ESP6500AA AF: 0.000761 AC: 2

ESP6500EA AF: 0.00164 AC: 9

ExAC AF: 0.000715 AC: 86

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	9.8
DANN	Benign	0.82
FATHMM_MKL	Pathogenic	0.98	D
PhyloP100		4.6
Vest4		0.18
GERP RS		5.3
PromoterAI		0.035	Neutral
Mutation Taster		=158/42	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs201820102; hg19: chrX-111003227;