12-38317056-C-G

Variant names:

• chr12-38317056-C-G
• NM_001013620.4:c.163C>G

Variant summary

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

The NM_001013620.4(ALG10B):​c.163C>G​(p.Leu55Val) 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. 13/21 in silico tools predict a benign 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: 0.680

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15194237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG10B	NM_001013620.4	c.163C>G	p.Leu55Val	missense_variant	Exon 1 of 3	ENST00000308742.9	NP_001013642.2
ALG10B	NM_001308340.2	c.163C>G	p.Leu55Val	missense_variant	Exon 1 of 3		NP_001295269.2
ALG10B	XM_005268665.5	c.-10+287C>G		intron_variant	Intron 1 of 2		XP_005268722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG10B	ENST00000308742.9	c.163C>G	p.Leu55Val	missense_variant	Exon 1 of 3	1	NM_001013620.4	ENSP00000310120.4
ALG10B	ENST00000548240.1	n.145+18C>G		intron_variant	Intron 1 of 2	1		ENSP00000449210.1
ALG10B	ENST00000551464.1	c.163C>G	p.Leu55Val	missense_variant	Exon 1 of 3	3		ENSP00000448819.1
ALG10B	ENST00000553138.1	n.290C>G		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.163C>G (p.L55V) alteration is located in exon 1 (coding exon 1) of the ALG10B gene. This alteration results from a C to G substitution at nucleotide position 163, causing the leucine (L) at amino acid position 55 to be replaced by a valine (V). 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	0.077
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00077	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.070
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.080	N;N
REVEL	Benign	0.086
Sift	Benign	0.054	T;D
Sift4G	Benign	0.16	T;T
Polyphen		0.16	B;.
Vest4		0.14
MutPred		0.61		Gain of catalytic residue at H52 (P = 0.0067);Gain of catalytic residue at H52 (P = 0.0067);
MVP		0.33
MPC		0.044
ClinPred		0.55	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.093
gMVP		0.49

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: chr12-38710858;