Genetic Variant ALG10B:p.Pro120Leu (chr12-38318448-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001013620.4(ALG10B):c.359C>T(p.Pro120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ALG10B
NM_001013620.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

Variant links:

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]

ALG10B links:

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ACMG classification

Classification made for transcript

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=0.08848789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG10B	NM_001013620.4 link	c.359C>T	p.Pro120Leu	missense_variant	Exon 2 of 3	ENST00000308742.9	NP_001013642.2	Q5I7T1
ALG10B	NM_001308340.2 link	c.359C>T	p.Pro120Leu	missense_variant	Exon 2 of 3		NP_001295269.2
ALG10B	XM_005268665.5 link	c.179C>T	p.Pro60Leu	missense_variant	Exon 2 of 3		XP_005268722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG10B	ENST00000308742.9 link	c.359C>T	p.Pro120Leu	missense_variant	Exon 2 of 3	1	NM_001013620.4	ENSP00000310120.4		Q5I7T1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251360

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461764

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.359C>T (p.P120L) alteration is located in exon 2 (coding exon 2) of the ALG10B gene. This alteration results from a C to T substitution at nucleotide position 359, causing the proline (P) at amino acid position 120 to be replaced by a leucine (L). 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

0.092

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.0061

T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.87

D;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.088

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.090

N;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.16

Sift

Benign

0.72

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.015

B;.

Vest4

0.084

MutPred

0.53

Loss of disorder (P = 0.0191);Loss of disorder (P = 0.0191);

MVP

0.64

MPC

0.044

ClinPred

0.096

GERP RS

3.7

Varity_R

0.14

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over