rs372841179

chrX-111759964-C-T

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.3379C>T(p.Pro1127Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000096 in 1,208,832 control chromosomes in the GnomAD database, including 4 homozygotes. There are 36 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 4 hem., cov: 22)
  • Exomes 𝑓: 0.000094 (4 hom. 32 hem.)
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0620

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016321748).
• BP6: Variant X-111759964-C-T is Benign according to our data. Variant chrX-111759964-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 540340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000117 (13/111465) while in subpopulation AFR AF= 0.000391 (12/30672). AF 95% confidence interval is 0.000225. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAdExome at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG13	NM_001099922.3	c.3379C>T	p.Pro1127Ser	missense_variant	27/27	ENST00000394780.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG13	ENST00000394780.8	c.3379C>T	p.Pro1127Ser	missense_variant	27/27	2	NM_001099922.3	A2

Frequencies

GnomAD3 genomes AF: 0.0000898 AC: 10 AN: 111415 Hom.: 0 Cov.: 22 AF XY: 0.0000298 AC XY: 1 AN XY: 33595

Gnomad AFR AF: 0.000294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000960

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: 0.0000393 AC: 7 AN: 178027 Hom.: 0 AF XY: 0.0000303 AC XY: 2 AN XY: 65989

Gnomad AFR exome AF: 0.000407

Gnomad AMR exome AF: 0.0000368

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: 0.000226

GnomAD4 exome AF: 0.0000939 AC: 103 AN: 1097367 Hom.: 4 Cov.: 30 AF XY: 0.0000882 AC XY: 32 AN XY: 362913

Gnomad4 AFR exome AF: 0.00144

Gnomad4 AMR exome AF: 0.0000570

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000370

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00130

GnomAD4 genome AF: 0.000117 AC: 13 AN: 111465 Hom.: 0 Cov.: 22 AF XY: 0.000119 AC XY: 4 AN XY: 33655

Gnomad4 AFR AF: 0.000391

Gnomad4 AMR AF: 0.0000959

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

Alfa AF: 0.0000680 Hom.: 0

Bravo AF: 0.000159

ExAC AF: 0.0000665 AC: 8

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	Fulgent Genetics, Fulgent Genetics	Oct 31, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 15, 2024	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.11
Dann	Benign	0.25
DEOGEN2	Benign	0.36	T;.;.;.;.
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.55	T;T;.;T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.016	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;.;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.2	N;.;N;.;.
REVEL	Benign	0.027
Sift	Benign	0.26	T;.;T;.;.
Sift4G	Benign	0.76	T;T;T;T;T
Polyphen		0.0020	B;B;B;B;B
Vest4		0.093
MVP		0.18
MPC		0.34
ClinPred		0.018	T
GERP RS		-3.1
Varity_R		0.033
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: rs372841179; hg19: chrX-111003192;