X-111681205-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001099922.3(ALG13):c.-14G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,209,568 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 93 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 0.00014 (0 hom., 4 hem., cov: 24)
  • Exomes 𝑓: 0.00024 (0 hom. 89 hem.)
• Consequence: ALG13 NM_001099922.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.408

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant X-111681205-G-A is Benign according to our data. Variant chrX-111681205-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 507735.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000142 (16/112761) while in subpopulation SAS AF= 0.000367 (1/2723). AF 95% confidence interval is 0.000102. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3	c.-14G>A		5_prime_UTR_variant	1/27	ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8	c.-14G>A		5_prime_UTR_variant	1/27	2	NM_001099922.3	A2

Frequencies

GnomAD3 genomes AF: 0.000142 AC: 16 AN: 112707 Hom.: 0 Cov.: 24 AF XY: 0.000115 AC XY: 4 AN XY: 34857

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000186

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000366

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000175 AC: 32 AN: 182913 Hom.: 0 AF XY: 0.000148 AC XY: 10 AN XY: 67385

Gnomad AFR exome AF: 0.0000761

Gnomad AMR exome AF: 0.000367

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000369

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000171

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000239 AC: 262 AN: 1096807 Hom.: 0 Cov.: 29 AF XY: 0.000246 AC XY: 89 AN XY: 362191

Gnomad4 AFR exome AF: 0.000152

Gnomad4 AMR exome AF: 0.000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000333

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000268

Gnomad4 OTH exome AF: 0.000109

GnomAD4 genome AF: 0.000142 AC: 16 AN: 112761 Hom.: 0 Cov.: 24 AF XY: 0.000115 AC XY: 4 AN XY: 34921

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000185

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000367

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000188

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000147

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	1.7
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs199642821; hg19: chrX-110924433;