X-111681212-C-T

Variant names:

• chrX-111681212-C-T
• rs188487746
• NM_001099922.3:c.-7C>T

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.-7C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 1,209,650 control chromosomes in the GnomAD database, including 1 homozygotes. There are 143 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 0.00033 (0 hom., 18 hem., cov: 24)
  • Exomes 𝑓: 0.00033 (1 hom. 125 hem.)
• Consequence: ALG13 NM_001099922.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant X-111681212-C-T is Benign according to our data. Variant chrX-111681212-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 385984.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000328 (37/112752) while in subpopulation NFE AF = 0.000413 (22/53238). AF 95% confidence interval is 0.000279. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 18 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG13	NM_001099922.3	c.-7C>T		5_prime_UTR_variant	Exon 1 of 27	ENST00000394780.8	NP_001093392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8	c.-7C>T		5_prime_UTR_variant	Exon 1 of 27	2	NM_001099922.3	ENSP00000378260.3

Frequencies

GnomAD3 genomes AF: 0.000328 AC: 37 AN: 112696 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000322

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00208

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000413

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000448 AC: 82 AN: 182870 AF XY: 0.000475

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000734

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00263

Gnomad NFE exome AF: 0.000453

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.000329 AC: 361 AN: 1096898 Hom.: 1 Cov.: 30 AF XY: 0.000345 AC XY: 125 AN XY: 362300

African (AFR) AF: 0.0000379 AC: 1 AN: 26378

American (AMR) AF: 0.00 AC: 0 AN: 35189

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19373

East Asian (EAS) AF: 0.00 AC: 0 AN: 30189

South Asian (SAS) AF: 0.00 AC: 0 AN: 54088

European-Finnish (FIN) AF: 0.00237 AC: 96 AN: 40513

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.000284 AC: 239 AN: 840982

Other (OTH) AF: 0.000543 AC: 25 AN: 46051

GnomAD4 genome AF: 0.000328 AC: 37 AN: 112752 Hom.: 0 Cov.: 24 AF XY: 0.000515 AC XY: 18 AN XY: 34918

African (AFR) AF: 0.0000321 AC: 1 AN: 31141

American (AMR) AF: 0.00 AC: 0 AN: 10775

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3541

South Asian (SAS) AF: 0.00 AC: 0 AN: 2722

European-Finnish (FIN) AF: 0.00208 AC: 13 AN: 6246

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

European-Non Finnish (NFE) AF: 0.000413 AC: 22 AN: 53238

Other (OTH) AF: 0.00 AC: 0 AN: 1532

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000166

EpiCase AF: 0.000382

EpiControl AF: 0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 10, 2017

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.6
DANN	Benign	0.87
PhyloP100		1.1
PromoterAI		-0.071	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: rs188487746; hg19: chrX-110924440;