rs200066623

Variant names:

• chrX-111736856-C-T
• rs200066623
• NM_001099922.3:c.2672C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001099922.3(ALG13):​c.2672C>T​(p.Ser891Phe) variant causes a missense change. The variant allele was found at a frequency of 0.003 in 1,206,632 control chromosomes in the GnomAD database, including 25 homozygotes. There are 1,256 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (1 hom., 183 hem., cov: 23)
  • Exomes 𝑓: 0.0029 (24 hom. 1073 hem.)
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 5.25
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038899481).
• BP6: Variant X-111736856-C-T is Benign according to our data. Variant chrX-111736856-C-T is described in ClinVar as Benign. ClinVar VariationId is 238293.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 = 0.00364 (408/112016) while in subpopulation NFE AF = 0.003 (160/53277). AF 95% confidence interval is 0.00262. There are 1 homozygotes in GnomAd4. There are 183 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 183 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.2672C>T	p.Ser891Phe	missense	Exon 23 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.2438C>T	p.Ser813Phe	missense	Exon 23 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.2672C>T	p.Ser891Phe	missense	Exon 23 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.2672C>T	p.Ser891Phe	missense	Exon 23 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.2648C>T	p.Ser883Phe	missense	Exon 23 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.2498C>T	p.Ser833Phe	missense	Exon 21 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes AF: 0.00364 AC: 408 AN: 111964 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.0000974

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000380

Gnomad ASJ AF: 0.00679

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00300

Gnomad OTH AF: 0.00265

GnomAD2 exomes AF: 0.00512 AC: 888 AN: 173528 AF XY: 0.00525

Gnomad AFR exome AF: 0.000249

Gnomad AMR exome AF: 0.00122

Gnomad ASJ exome AF: 0.00677

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0386

Gnomad NFE exome AF: 0.00224

Gnomad OTH exome AF: 0.00468

GnomAD4 exome AF: 0.00294 AC: 3215 AN: 1094616 Hom.: 24 Cov.: 29 AF XY: 0.00298 AC XY: 1073 AN XY: 360300

African (AFR) AF: 0.000343 AC: 9 AN: 26263

American (AMR) AF: 0.00109 AC: 38 AN: 34821

Ashkenazi Jewish (ASJ) AF: 0.00696 AC: 134 AN: 19262

East Asian (EAS) AF: 0.00 AC: 0 AN: 30033

South Asian (SAS) AF: 0.0000375 AC: 2 AN: 53266

European-Finnish (FIN) AF: 0.0366 AC: 1480 AN: 40463

Middle Eastern (MID) AF: 0.00121 AC: 5 AN: 4122

European-Non Finnish (NFE) AF: 0.00165 AC: 1389 AN: 840444

Other (OTH) AF: 0.00344 AC: 158 AN: 45942

GnomAD4 genome AF: 0.00364 AC: 408 AN: 112016 Hom.: 1 Cov.: 23 AF XY: 0.00535 AC XY: 183 AN XY: 34186

African (AFR) AF: 0.0000972 AC: 3 AN: 30866

American (AMR) AF: 0.000380 AC: 4 AN: 10537

Ashkenazi Jewish (ASJ) AF: 0.00679 AC: 18 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.00 AC: 0 AN: 2672

European-Finnish (FIN) AF: 0.0363 AC: 219 AN: 6028

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

European-Non Finnish (NFE) AF: 0.00300 AC: 160 AN: 53277

Other (OTH) AF: 0.00261 AC: 4 AN: 1531

Alfa AF: 0.00229 Hom.: 110

Bravo AF: 0.00108

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000692 AC: 2

ESP6500AA AF: 0.000381 AC: 1

ESP6500EA AF: 0.00127 AC: 7

ExAC AF: 0.00406 AC: 489

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	D
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0039	T
MetaSVM	Uncertain	-0.069	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.3
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.26
MVP		0.67
MPC		0.56
ClinPred		0.030	T
GERP RS		5.5
Varity_R		0.63
gMVP		0.24
Mutation Taster		=91/9	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs200066623; hg19: chrX-110980084;