rs146925326

chrX-111682233-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001099922.3(ALG13):c.183C>T(p.Tyr61=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,197,624 control chromosomes in the GnomAD database, including 139 homozygotes. There are 5,188 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (12 hom., 281 hem., cov: 23)
  • Exomes 𝑓: 0.015 (127 hom. 4907 hem.)
• Consequence: ALG13 NM_001099922.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.657

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0039321184).
• BP6: Variant X-111682233-C-T is Benign according to our data. Variant chrX-111682233-C-T is described in ClinVar as [Benign]. Clinvar id is 238290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111682233-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.657 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00923 (1035/112115) while in subpopulation NFE AF= 0.0165 (877/53223). AF 95% confidence interval is 0.0156. There are 12 homozygotes in gnomad4. There are 281 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3	c.183C>T	p.Tyr61=	synonymous_variant	2/27	ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8	c.183C>T	p.Tyr61=	synonymous_variant	2/27	2	NM_001099922.3	A2

Frequencies

GnomAD3 genomes AF: 0.00925 AC: 1036 AN: 112060 Hom.: 12 Cov.: 23 AF XY: 0.00824 AC XY: 282 AN XY: 34228

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00198

Gnomad ASJ AF: 0.00264

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00114

Gnomad FIN AF: 0.00850

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.00397

GnomAD3 exomes AF: 0.00809 AC: 1393 AN: 172113 Hom.: 9 AF XY: 0.00763 AC XY: 441 AN XY: 57779

Gnomad AFR exome AF: 0.00207

Gnomad AMR exome AF: 0.00305

Gnomad ASJ exome AF: 0.000990

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00126

Gnomad FIN exome AF: 0.00824

Gnomad NFE exome AF: 0.0142

Gnomad OTH exome AF: 0.00555

GnomAD4 exome AF: 0.0146 AC: 15858 AN: 1085509 Hom.: 127 Cov.: 29 AF XY: 0.0139 AC XY: 4907 AN XY: 352453

Gnomad4 AFR exome AF: 0.00196

Gnomad4 AMR exome AF: 0.00311

Gnomad4 ASJ exome AF: 0.00199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00129

Gnomad4 FIN exome AF: 0.00892

Gnomad4 NFE exome AF: 0.0176

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.00923 AC: 1035 AN: 112115 Hom.: 12 Cov.: 23 AF XY: 0.00819 AC XY: 281 AN XY: 34293

Gnomad4 AFR AF: 0.00223

Gnomad4 AMR AF: 0.00198

Gnomad4 ASJ AF: 0.00264

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00114

Gnomad4 FIN AF: 0.00850

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.00392

Alfa AF: 0.00959 Hom.: 82

Bravo AF: 0.00844

TwinsUK AF: 0.0208 AC: 77

ALSPAC AF: 0.0145 AC: 42

ESP6500AA AF: 0.00104 AC: 4

ESP6500EA AF: 0.0162 AC: 109

ExAC AF: 0.00893 AC: 1084

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 36 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 14, 2016

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. -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 14, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Mar 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	13
Dann	Benign	0.52
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0039	T
MutationTaster	Benign	1.0	D;D;D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.082	B
Vest4		0.049
MVP		0.49
GERP RS		4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs146925326; hg19: chrX-110925461;