12-34026298-G-C

Variant names:

• chr12-34026298-G-C
• rs185875444
• NM_032834.4:c.805G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032834.4(ALG10):​c.805G>C​(p.Val269Leu) 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. 17/22 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. V269I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALG10 NM_032834.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 0 publications found

Genes affected

ALG10 (HGNC:23162): (ALG10 alpha-1,2-glucosyltransferase) This gene encodes a membrane-associated protein that adds the third glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. That is, it transfers the terminal glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Glc2Man9GlcNAc(2)-PP-Dol. The rat protein homolog was shown to specifically modulate the gating function of the rat neuronal ether-a-go-go (EAG) potassium ion channel. [provided by RefSeq, Jan 2010]

ALG10 Gene-Disease associations (from GenCC):

• congenital disorder of glycosylation

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000245482 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0661124).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032834.4. 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
	ALG10	NM_032834.4	MANE Select	c.805G>C	p.Val269Leu	missense	Exon 3 of 3	NP_116223.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG10	ENST00000266483.7	TSL:1 MANE Select	c.805G>C	p.Val269Leu	missense	Exon 3 of 3	ENSP00000266483.2	Q5BKT4
	ALG10	ENST00000541875.1	TSL:1	n.*545G>C		non_coding_transcript_exon	Exon 3 of 3	ENSP00000443142.1	F5H5T2
	ALG10	ENST00000541875.1	TSL:1	n.*545G>C		3_prime_UTR	Exon 3 of 3	ENSP00000443142.1	F5H5T2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.95
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.040
Sift	Benign	0.43	T
Sift4G	Benign	0.53	T
Polyphen		0.0050	B
Vest4		0.027
MutPred		0.51		Gain of catalytic residue at A266 (P = 0)
MVP		0.45
MPC		0.19
ClinPred		0.054	T
GERP RS		2.5
Varity_R		0.084
gMVP		0.38
Mutation Taster		=92/8	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: rs185875444; hg19: chr12-34179233;