11-78100967-T-G

Variant names:

• chr11-78100967-T-G
• rs479612
• NM_024079.5:c.1578A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024079.5(ALG8):​c.1578A>C​(p.Gln526His) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q526Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ALG8 NM_024079.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389

Genes affected

ALG8 (HGNC:23161): (ALG8 alpha-1,3-glucosyltransferase) This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins. Mutations in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ih). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09063825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG8	NM_024079.5	c.1578A>C	p.Gln526His	missense_variant	Exon 13 of 13	ENST00000299626.10	NP_076984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG8	ENST00000299626.10	c.1578A>C	p.Gln526His	missense_variant	Exon 13 of 13	1	NM_024079.5	ENSP00000299626.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	6.6
DANN	Benign	0.79
DEOGEN2	Benign	0.068	T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.098
Sift	Benign	0.29	T;T
Sift4G	Uncertain	0.025	D;D
Polyphen		0.0	B;.
Vest4		0.22
MutPred		0.29		Loss of methylation at K524 (P = 0.0587);.;
MVP		0.35
MPC		0.14
ClinPred		0.069	T
GERP RS		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.030
gMVP		0.33

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: rs479612; hg19: chr11-77812013;