rs3027818

Positions:

• chrX-111757672-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001099922.3(ALG13):​c.3058A>G​(p.Thr1020Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,207,107 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 190 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., 9 hem., cov: 22)
  • Exomes 𝑓: 0.00028 (0 hom. 181 hem.)
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.698

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034748316).
• BP6: Variant X-111757672-A-G is Benign according to our data. Variant chrX-111757672-A-G is described in ClinVar as [Benign]. Clinvar id is 412612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-111757672-A-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000108 (12/111041) while in subpopulation SAS AF= 0.00348 (9/2589). AF 95% confidence interval is 0.00181. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG13	NM_001099922.3	c.3058A>G	p.Thr1020Ala	missense_variant	26/27	ENST00000394780.8	NP_001093392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8	c.3058A>G	p.Thr1020Ala	missense_variant	26/27	2	NM_001099922.3	ENSP00000378260.3

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 12 AN: 110991 Hom.: 0 Cov.: 22 AF XY: 0.000271 AC XY: 9 AN XY: 33175

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000759

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00347

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000673

GnomAD3 exomes AF: 0.000595 AC: 106 AN: 178107 Hom.: 0 AF XY: 0.000908 AC XY: 60 AN XY: 66057

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000405

Gnomad EAS exome AF: 0.0000744

Gnomad SAS exome AF: 0.00513

Gnomad FIN exome AF: 0.0000629

Gnomad NFE exome AF: 0.0000127

Gnomad OTH exome AF: 0.000680

GnomAD4 exome AF: 0.000282 AC: 309 AN: 1096066 Hom.: 0 Cov.: 30 AF XY: 0.000501 AC XY: 181 AN XY: 361630

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000310

Gnomad4 EAS exome AF: 0.0000332

Gnomad4 SAS exome AF: 0.00485

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000143

Gnomad4 OTH exome AF: 0.000543

GnomAD4 genome AF: 0.000108 AC: 12 AN: 111041 Hom.: 0 Cov.: 22 AF XY: 0.000271 AC XY: 9 AN XY: 33235

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000759

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00348

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000665

Alfa AF: 0.0000805 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.000747 AC: 90

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 36 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.65
DEOGEN2	Benign	0.21	T;.;.;.;.
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.49	T;T;.;T;.
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.0035	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L;.;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.98	N;.;N;.;.
REVEL	Benign	0.023
Sift	Benign	0.34	T;.;T;.;.
Sift4G	Benign	0.50	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.049
MutPred		0.42		Loss of glycosylation at T1020 (P = 0.004);.;.;.;.;
MVP		0.15
MPC		0.17
ClinPred		0.0072	T
GERP RS		-4.1
Varity_R		0.050
gMVP		0.14

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3027818; hg19: chrX-111000900;