chr12-34024080-G-A

Position:

• chr12-34024080-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000266483.7(ALG10):​c.290G>A​(p.Arg97Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALG10 ENST00000266483.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.52

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG10	NM_032834.4	c.290G>A	p.Arg97Lys	missense_variant	2/3	ENST00000266483.7	NP_116223.3
ALG10	XM_024449230.2	c.110G>A	p.Arg37Lys	missense_variant	2/3		XP_024304998.1
ALG10	XM_024449231.2	c.110G>A	p.Arg37Lys	missense_variant	2/3		XP_024304999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG10	ENST00000266483.7	c.290G>A	p.Arg97Lys	missense_variant	2/3	1	NM_032834.4	ENSP00000266483	P1
	ENST00000501954.2	n.380C>T		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.290G>A (p.R97K) alteration is located in exon 2 (coding exon 2) of the ALG10 gene. This alteration results from a G to A substitution at nucleotide position 290, causing the arginine (R) at amino acid position 97 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;.
Eigen	Pathogenic	0.78
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Pathogenic	3.9	H;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.96
MutPred		0.78		Gain of catalytic residue at I93 (P = 0.0034);Gain of catalytic residue at I93 (P = 0.0034);
MVP		0.77
MPC		0.76
ClinPred		1.0	D
GERP RS		3.6
Varity_R		0.88
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-34177015;