X-111759806-A-G

Position:

• chrX-111759806-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.3221A>G​(p.Tyr1074Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,208,181 control chromosomes in the GnomAD database, including 1 homozygotes. There are 191 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 0.00012 (0 hom., 6 hem., cov: 23)
  • Exomes 𝑓: 0.00032 (1 hom. 185 hem.)
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.96

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=0.0063561797).
• BP6: Variant X-111759806-A-G is Benign according to our data. Variant chrX-111759806-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 381527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000117 (13/111288) while in subpopulation SAS AF= 0.00421 (11/2610). AF 95% confidence interval is 0.00236. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG13	NM_001099922.3	c.3221A>G	p.Tyr1074Cys	missense_variant	27/27	ENST00000394780.8	NP_001093392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG13	ENST00000394780.8	c.3221A>G	p.Tyr1074Cys	missense_variant	27/27	2	NM_001099922.3	ENSP00000378260.3

Frequencies

GnomAD3 genomes AF: 0.000117 AC: 13 AN: 111233 Hom.: 0 Cov.: 23 AF XY: 0.000179 AC XY: 6 AN XY: 33445

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00420

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.000675

GnomAD3 exomes AF: 0.000635 AC: 112 AN: 176489 Hom.: 0 AF XY: 0.00101 AC XY: 65 AN XY: 64569

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00583

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000257

Gnomad OTH exome AF: 0.000458

GnomAD4 exome AF: 0.000317 AC: 348 AN: 1096893 Hom.: 1 Cov.: 30 AF XY: 0.000510 AC XY: 185 AN XY: 362491

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000332

Gnomad4 SAS exome AF: 0.00575

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000119

Gnomad4 OTH exome AF: 0.000565

GnomAD4 genome AF: 0.000117 AC: 13 AN: 111288 Hom.: 0 Cov.: 23 AF XY: 0.000179 AC XY: 6 AN XY: 33510

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00421

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000189

Gnomad4 OTH AF: 0.000666

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.000798 AC: 96

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 36 Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 02, 2019

This variant is associated with the following publications: (PMID: 24501762, 28887793, 28940310, 25732998) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.64	D;.;.;.;.
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.78	T;T;.;T;.
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.0064	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L;.;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.0	D;.;D;.;.
REVEL	Benign	0.083
Sift	Benign	0.13	T;.;T;.;.
Sift4G	Benign	0.16	T;T;T;T;T
Polyphen		0.25	B;B;P;P;P
Vest4		0.19
MutPred		0.26		Loss of phosphorylation at Y1074 (P = 0.0108);.;.;.;.;
MVP		0.53
MPC		0.22
ClinPred		0.036	T
GERP RS		3.4
Varity_R		0.41
gMVP		0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs372990620; hg19: chrX-111003034;