rs371239344

Variant names:

• chrX-111727425-T-C
• rs371239344
• NM_001099922.3:c.2070T>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.2070T>C​(p.Asp690Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,203,073 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 62 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 0.00013 (0 hom., 3 hem., cov: 23)
  • Exomes 𝑓: 0.00018 (0 hom. 59 hem.)
• Consequence: ALG13 NM_001099922.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.374
• 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=-0.56).
• BP6: Variant X-111727425-T-C is Benign according to our data. Variant chrX-111727425-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 388244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.374 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000134 (15/112052) while in subpopulation NFE AF = 0.000263 (14/53222). AF 95% confidence interval is 0.000159. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3	c.2070T>C	p.Asp690Asp	synonymous_variant	Exon 17 of 27	ENST00000394780.8	NP_001093392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8	c.2070T>C	p.Asp690Asp	synonymous_variant	Exon 17 of 27	2	NM_001099922.3	ENSP00000378260.3

Frequencies

GnomAD3 genomes AF: 0.000134 AC: 15 AN: 112052 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000324

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: 0.000263

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000459 AC: 8 AN: 174466 AF XY: 0.0000640

Gnomad AFR exome AF: 0.0000832

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000909

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000176 AC: 192 AN: 1091021 Hom.: 0 Cov.: 29 AF XY: 0.000165 AC XY: 59 AN XY: 356649

African (AFR) AF: 0.0000761 AC: 2 AN: 26283

American (AMR) AF: 0.00 AC: 0 AN: 35033

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19305

East Asian (EAS) AF: 0.00 AC: 0 AN: 30131

South Asian (SAS) AF: 0.00 AC: 0 AN: 53260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.000224 AC: 187 AN: 836570

Other (OTH) AF: 0.0000654 AC: 3 AN: 45877

GnomAD4 genome AF: 0.000134 AC: 15 AN: 112052 Hom.: 0 Cov.: 23 AF XY: 0.0000877 AC XY: 3 AN XY: 34204

African (AFR) AF: 0.0000324 AC: 1 AN: 30825

American (AMR) AF: 0.00 AC: 0 AN: 10570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3585

South Asian (SAS) AF: 0.00 AC: 0 AN: 2624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000263 AC: 14 AN: 53222

Other (OTH) AF: 0.00 AC: 0 AN: 1518

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000117

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 36 Benign:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Aug 14, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.9
DANN	Benign	0.48
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs371239344; hg19: chrX-110970653;