13-52012423-C-G

Variant names:

• chr13-52012423-C-G
• rs1363416785
• NM_001004127.3:c.5C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004127.3(ALG11):​c.5C>G​(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALG11 NM_001004127.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 0 publications found

Genes affected

ALG11 (HGNC:32456): (ALG11 alpha-1,2-mannosyltransferase) This gene encodes a GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase which is localized to the cytosolic side of the endoplasmic reticulum (ER) and catalyzes the transfer of the fourth and fifth mannose residue from GDP-mannose (GDP-Man) to Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol resulting in the production of Man5GlcNAc2-PP-dolichol. Mutations in this gene are associated with congenital disorder of glycosylation type Ip (CDGIP). This gene overlaps but is distinct from the UTP14, U3 small nucleolar ribonucleoprotein, homolog C (yeast) gene. A pseudogene of the GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase has been identified on chromosome 19. [provided by RefSeq, Aug 2010]

ALG11 Gene-Disease associations (from GenCC):

• ALG11-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3772944).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004127.3. 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
	ALG11	NM_001004127.3	MANE Select	c.5C>G	p.Ala2Gly	missense	Exon 1 of 4	NP_001004127.2	Q2TAA5
	ALG11	NR_036571.3		n.26C>G		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG11	ENST00000521508.2	TSL:1 MANE Select	c.5C>G	p.Ala2Gly	missense	Exon 1 of 4	ENSP00000430236.1	Q2TAA5
	ALG11	ENST00000649340.2		c.5C>G	p.Ala2Gly	missense	Exon 1 of 4	ENSP00000497184.2	A0A3B3IS90
	ALG11	ENST00000681053.1		c.5C>G	p.Ala2Gly	missense	Exon 1 of 3	ENSP00000505307.1	A0A7P0T8Y4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.060	T
Eigen	Benign	0.013
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.9
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.20
Sift	Benign	0.043	D
Sift4G	Benign	0.087	T
Polyphen		0.68	P
Vest4		0.42
MutPred		0.24		Gain of catalytic residue at A3 (P = 0)
MVP		0.83
MPC		0.063
ClinPred		0.96	D
GERP RS		4.2
PromoterAI		-0.94	Under-expression
Varity_R		0.11
gMVP		0.51
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1363416785; hg19: chr13-52586559;