NM_001004127.3:c.5C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG11	NM_001004127.3	c.5C>G	p.Ala2Gly	missense_variant	Exon 1 of 4	ENST00000521508.2	NP_001004127.2
ALG11	NR_036571.3	n.26C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG11	ENST00000521508.2	c.5C>G	p.Ala2Gly	missense_variant	Exon 1 of 4	1	NM_001004127.3	ENSP00000430236.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.8	.;.;L
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.0	D;.;N
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);Gain of catalytic residue at A3 (P = 0);Gain of catalytic residue at A3 (P = 0);
MVP		0.83
MPC		0.063
ClinPred		0.96	D
GERP RS		4.2
Varity_R		0.11
gMVP		0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs1363416785; hg19: chr13-52586559;