chrX-111744768-ACCTCCTCCTCCTCCTCCT-A

Variant names:

• chrX-111744768-ACCTCCTCCTCCTCCTCCT-A
• rs56717389
• NM_001099922.3:c.2818_2835delCCTCCTCCTCCTCCTCCT

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001099922.3(ALG13):​c.2818_2835delCCTCCTCCTCCTCCTCCT​(p.Pro940_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 0.000032 in 594,555 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P940P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., 0 hem., cov: 9)
  • Exomes 𝑓: 0.000029 (0 hom. 5 hem.)
• Consequence: ALG13 NM_001099922.3 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.322
• 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: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001099922.3
• BS2: High Hemizygotes in GnomAdExome4 at 5 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.2818_2835delCCTCCTCCTCCTCCTCCT	p.Pro940_Pro945del	conservative_inframe_deletion	Exon 24 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.2584_2601delCCTCCTCCTCCTCCTCCT	p.Pro862_Pro867del	conservative_inframe_deletion	Exon 24 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.2695+7911_2695+7928delCCTCCTCCTCCTCCTCCT		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.2818_2835delCCTCCTCCTCCTCCTCCT	p.Pro940_Pro945del	conservative_inframe_deletion	Exon 24 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.2794_2811delCCTCCTCCTCCTCCTCCT	p.Pro932_Pro937del	conservative_inframe_deletion	Exon 24 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.2644_2661delCCTCCTCCTCCTCCTCCT	p.Pro882_Pro887del	conservative_inframe_deletion	Exon 22 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes AF: 0.0000807 AC: 3 AN: 37161 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.000101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000100

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000287 AC: 16 AN: 557394 Hom.: 0 AF XY: 0.0000315 AC XY: 5 AN XY: 158562

African (AFR) AF: 0.000138 AC: 2 AN: 14463

American (AMR) AF: 0.0000605 AC: 1 AN: 16521

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9525

East Asian (EAS) AF: 0.00 AC: 0 AN: 15385

South Asian (SAS) AF: 0.0000424 AC: 1 AN: 23599

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1547

European-Non Finnish (NFE) AF: 0.0000277 AC: 12 AN: 433347

Other (OTH) AF: 0.00 AC: 0 AN: 24413

GnomAD4 genome AF: 0.0000807 AC: 3 AN: 37161 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 7145

African (AFR) AF: 0.000101 AC: 1 AN: 9937

American (AMR) AF: 0.00 AC: 0 AN: 2509

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 540

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 91

European-Non Finnish (NFE) AF: 0.000100 AC: 2 AN: 19920

Other (OTH) AF: 0.00 AC: 0 AN: 425

Alfa AF: 0.00 Hom.: 38

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy, 36 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32

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;