X-111744768-ACCTCCTCCTCCTCCTCCTCCTCCT-ACCTCCTCCTCCTCCT

Variant names:

• chrX-111744768-ACCTCCTCCT-A
• rs56717389
• NM_001099922.3:c.2827_2835delCCTCCTCCT

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_001099922.3(ALG13):​c.2827_2835delCCTCCTCCT​(p.Pro943_Pro945del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000202 in 594,303 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., 0 hem., cov: 9)
  • Exomes 𝑓: 0.00020 (0 hom. 28 hem.)
• Consequence: ALG13 NM_001099922.3 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.290
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001099922.3
• BP6: Variant X-111744768-ACCTCCTCCT-A is Benign according to our data. Variant chrX-111744768-ACCTCCTCCT-A is described in ClinVar as Likely_benign. ClinVar VariationId is 648499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000215 (8/37156) while in subpopulation SAS AF = 0.00186 (1/537). AF 95% confidence interval is 0.000198. There are 0 homozygotes in GnomAd4. There are 0 alleles in the male GnomAd4 subpopulation. Median coverage is 9. This position passed quality control check.
• BS2: High Hemizygotes in GnomAdExome4 at 28 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.2827_2835delCCTCCTCCT	p.Pro943_Pro945del	conservative_inframe_deletion	Exon 24 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.2593_2601delCCTCCTCCT	p.Pro865_Pro867del	conservative_inframe_deletion	Exon 24 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.2695+7920_2695+7928delCCTCCTCCT		intron	N/A	NP_001311221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	ENST00000394780.8	TSL:2 MANE Select	c.2827_2835delCCTCCTCCT	p.Pro943_Pro945del	conservative_inframe_deletion	Exon 24 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.2803_2811delCCTCCTCCT	p.Pro935_Pro937del	conservative_inframe_deletion	Exon 24 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.2653_2661delCCTCCTCCT	p.Pro885_Pro887del	conservative_inframe_deletion	Exon 22 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes AF: 0.000215 AC: 8 AN: 37160 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.000503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000399

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00185

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000502

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000201 AC: 112 AN: 557147 Hom.: 0 AF XY: 0.000177 AC XY: 28 AN XY: 158423

African (AFR) AF: 0.000207 AC: 3 AN: 14460

American (AMR) AF: 0.000787 AC: 13 AN: 16512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9524

East Asian (EAS) AF: 0.000130 AC: 2 AN: 15380

South Asian (SAS) AF: 0.000721 AC: 17 AN: 23565

European-Finnish (FIN) AF: 0.000108 AC: 2 AN: 18591

Middle Eastern (MID) AF: 0.000646 AC: 1 AN: 1547

European-Non Finnish (NFE) AF: 0.000162 AC: 70 AN: 433166

Other (OTH) AF: 0.000164 AC: 4 AN: 24402

GnomAD4 genome AF: 0.000215 AC: 8 AN: 37156 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 7144

African (AFR) AF: 0.000503 AC: 5 AN: 9936

American (AMR) AF: 0.000397 AC: 1 AN: 2520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1002

East Asian (EAS) AF: 0.00 AC: 0 AN: 1208

South Asian (SAS) AF: 0.00186 AC: 1 AN: 537

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 78

European-Non Finnish (NFE) AF: 0.0000502 AC: 1 AN: 19917

Other (OTH) AF: 0.00 AC: 0 AN: 429

Alfa AF: 0.00 Hom.: 38

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.29
Mutation Taster		=194/6	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs56717389; hg19: chrX-110987996;