12-38320297-A-G

Variant names:

• chr12-38320297-A-G
• NM_001013620.4:c.506A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001013620.4(ALG10B):​c.506A>G​(p.Tyr169Cys) 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: ALG10B NM_001013620.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.85

Genes affected

ALG10B (HGNC:31088): (ALG10 alpha-1,2-glucosyltransferase B) Enables transferase activity. Involved in positive regulation of inward rectifier potassium channel activity; positive regulation of protein glycosylation; and protein glycosylation. Located in endoplasmic reticulum. Implicated in long QT syndrome 2. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG10B	NM_001013620.4	c.506A>G	p.Tyr169Cys	missense_variant	Exon 3 of 3	ENST00000308742.9	NP_001013642.2
ALG10B	XM_005268665.5	c.326A>G	p.Tyr109Cys	missense_variant	Exon 3 of 3		XP_005268722.1
ALG10B	NM_001308340.2	c.369+1839A>G		intron_variant	Intron 2 of 2		NP_001295269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG10B	ENST00000308742.9	c.506A>G	p.Tyr169Cys	missense_variant	Exon 3 of 3	1	NM_001013620.4	ENSP00000310120.4

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

Mar 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.506A>G (p.Y169C) alteration is located in exon 3 (coding exon 3) of the ALG10B gene. This alteration results from a A to G substitution at nucleotide position 506, causing the tyrosine (Y) at amino acid position 169 to be replaced by a cysteine (C). 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	Benign	0.15
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.39
Sift	Benign	0.055	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.75
MutPred		0.53		Gain of catalytic residue at K173 (P = 0);
MVP		0.81
MPC		0.31
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.54
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-38714099;