X-111708031-C-G

Variant names:

• chrX-111708031-C-G
• rs1381653955
• NM_001099922.3:c.388C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099922.3(ALG13):​c.388C>G​(p.Leu130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000896 in 111,602 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L130P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: ALG13 NM_001099922.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.233
• Publications: 4 publications found

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-AS1 (HGNC:41277): (ALG13 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1201067).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099922.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	NM_001099922.3	MANE Select	c.388C>G	p.Leu130Val	missense	Exon 4 of 27	NP_001093392.1	Q9NP73-1
	ALG13	NM_001257231.2		c.154C>G	p.Leu52Val	missense	Exon 4 of 27	NP_001244160.1	Q9NP73-3
	ALG13	NM_001324292.2		c.388C>G	p.Leu130Val	missense	Exon 4 of 26	NP_001311221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG13	ENST00000394780.8	TSL:2 MANE Select	c.388C>G	p.Leu130Val	missense	Exon 4 of 27	ENSP00000378260.3	Q9NP73-1
	ALG13	ENST00000927365.1		c.388C>G	p.Leu130Val	missense	Exon 4 of 27	ENSP00000597424.1
	ALG13	ENST00000927366.1		c.388C>G	p.Leu130Val	missense	Exon 4 of 25	ENSP00000597425.1

Frequencies

GnomAD3 genomes AF: 0.00000896 AC: 1 AN: 111602 Hom.: 0 Cov.: 22

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000183 AC: 2 AN: 1092986 Hom.: 0 Cov.: 31 AF XY: 0.00000279 AC XY: 1 AN XY: 358950

African (AFR) AF: 0.00 AC: 0 AN: 26330

American (AMR) AF: 0.00 AC: 0 AN: 34859

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19138

East Asian (EAS) AF: 0.00 AC: 0 AN: 30136

South Asian (SAS) AF: 0.00 AC: 0 AN: 53087

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40063

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4042

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 839439

Other (OTH) AF: 0.00 AC: 0 AN: 45892

GnomAD4 genome AF: 0.00000896 AC: 1 AN: 111602 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33778

African (AFR) AF: 0.00 AC: 0 AN: 30694

American (AMR) AF: 0.00 AC: 0 AN: 10475

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3539

South Asian (SAS) AF: 0.00 AC: 0 AN: 2664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53166

Other (OTH) AF: 0.00 AC: 0 AN: 1480

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Developmental and epileptic encephalopathy, 36 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	3.2
DANN	Benign	0.79
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.23
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.10
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.037	D
Polyphen		0.080	B
Vest4		0.13
MVP		0.79
MPC		0.27
ClinPred		0.20	T
GERP RS		-0.45
Varity_R		0.099
gMVP		0.14
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1381653955; hg19: chrX-110951259; COSMIC: COSV99322989;