X-111681210-A-G

Variant names:

• chrX-111681210-A-G
• rs374253660
• NM_001099922.3:c.-9A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_001099922.3(ALG13):​c.-9A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000537 in 1,207,791 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 202 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 0.00023 (0 hom., 10 hem., cov: 24)
  • Exomes 𝑓: 0.00057 (0 hom. 192 hem.)
• Consequence: ALG13 NM_001099922.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.08
• 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: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant X-111681210-A-G is Benign according to our data. Variant chrX-111681210-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 387664.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000234 (26/111293) while in subpopulation SAS AF = 0.000759 (2/2634). AF 95% confidence interval is 0.000266. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 10 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.-9A>G		5_prime_UTR	Exon 1 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.-309A>G		5_prime_UTR	Exon 1 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.-9A>G		5_prime_UTR	Exon 1 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.-9A>G		5_prime_UTR	Exon 1 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000371979.7	TSL:1	c.-9A>G		5_prime_UTR	Exon 1 of 4	ENSP00000361047.3	Q9NP73-2
	ALG13	ENST00000927365.1		c.-9A>G		5_prime_UTR	Exon 1 of 27	ENSP00000597424.1

Frequencies

GnomAD3 genomes AF: 0.000234 AC: 26 AN: 111293 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000980

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000759

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000398

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000285 AC: 52 AN: 182745 AF XY: 0.000238

Gnomad AFR exome AF: 0.000305

Gnomad AMR exome AF: 0.000184

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000626

Gnomad NFE exome AF: 0.000453

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000567 AC: 622 AN: 1096498 Hom.: 0 Cov.: 29 AF XY: 0.000531 AC XY: 192 AN XY: 361918

African (AFR) AF: 0.0000758 AC: 2 AN: 26369

American (AMR) AF: 0.000114 AC: 4 AN: 35158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19366

East Asian (EAS) AF: 0.00 AC: 0 AN: 30161

South Asian (SAS) AF: 0.000444 AC: 24 AN: 54046

European-Finnish (FIN) AF: 0.0000494 AC: 2 AN: 40508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.000663 AC: 557 AN: 840714

Other (OTH) AF: 0.000717 AC: 33 AN: 46045

GnomAD4 genome AF: 0.000234 AC: 26 AN: 111293 Hom.: 0 Cov.: 24 AF XY: 0.000297 AC XY: 10 AN XY: 33693

African (AFR) AF: 0.0000980 AC: 3 AN: 30618

American (AMR) AF: 0.00 AC: 0 AN: 10648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2628

East Asian (EAS) AF: 0.00 AC: 0 AN: 3500

South Asian (SAS) AF: 0.000759 AC: 2 AN: 2634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.000398 AC: 21 AN: 52817

Other (OTH) AF: 0.00 AC: 0 AN: 1483

Alfa AF: 0.000391 Hom.: 2

Bravo AF: 0.000264

EpiCase AF: 0.000655

EpiControl AF: 0.000416

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	ALG13-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		2.1
PromoterAI		-0.0028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs374253660; hg19: chrX-110924438;