rs766772102

chrX-111727001-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001099922.3(ALG13):c.1922A>G(p.His641Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,209,507 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H641D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000021 (0 hom. 7 hem.)
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.30

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08782667).
• BP6: Variant X-111727001-A-G is Benign according to our data. Variant chrX-111727001-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 383125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000209 (23/1097871) while in subpopulation AMR AF= 0.000596 (21/35207). AF 95% confidence interval is 0.000399. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAdExome at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3	c.1922A>G	p.His641Arg	missense_variant	16/27	ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8	c.1922A>G	p.His641Arg	missense_variant	16/27	2	NM_001099922.3	A2

Frequencies

GnomAD3 genomes AF: 0.00000896 AC: 1 AN: 111636 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33820

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000950

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000101 AC: 18 AN: 179073 Hom.: 0 AF XY: 0.0000897 AC XY: 6 AN XY: 66873

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000621

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000225

GnomAD4 exome AF: 0.0000209 AC: 23 AN: 1097871 Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 7 AN XY: 363315

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000596

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000434

GnomAD4 genome AF: 0.00000896 AC: 1 AN: 111636 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33820

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000950

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000378

ExAC AF: 0.0000249 AC: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 36 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 27, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jan 24, 2022	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.59	D;.;.;.;.;T
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.69	T;T;.;T;.;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.088	T;T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.9	L;.;.;.;.;.
MutationTaster	Benign	0.85	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.9	D;.;D;.;.;.
REVEL	Benign	0.089
Sift	Benign	0.043	D;.;D;.;.;.
Sift4G	Uncertain	0.0080	D;D;T;T;T;T
Polyphen		0.77	P;P;P;P;P;.
Vest4		0.43
MutPred		0.40		Gain of MoRF binding (P = 0.0677);.;.;.;.;.;
MVP		0.61
MPC		0.28
ClinPred		0.12	T
GERP RS		4.4
Varity_R		0.38
gMVP		0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs766772102; hg19: chrX-110970229;