Genetic Variant ALG10B:p.Met36Leu (chr12-38316999-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001013620.4(ALG10B):c.106A>T(p.Met36Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,613,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

ALG10B
NM_001013620.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG10B	NM_001013620.4 link	c.106A>T	p.Met36Leu	missense_variant	Exon 1 of 3	ENST00000308742.9	NP_001013642.2	Q5I7T1
ALG10B	NM_001308340.2 link	c.106A>T	p.Met36Leu	missense_variant	Exon 1 of 3		NP_001295269.2
ALG10B	XM_005268665.5 link	c.-10+230A>T		intron_variant	Intron 1 of 2		XP_005268722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ALG10B	ENST00000308742.9 link	c.106A>T	p.Met36Leu	missense_variant	Exon 1 of 3	1	NM_001013620.4	ENSP00000310120.4	Q5I7T1
ALG10B	ENST00000548240.1 link	n.106A>T		non_coding_transcript_exon_variant	Exon 1 of 3	1		ENSP00000449210.1	F8VWA9
ALG10B	ENST00000551464.1 link	c.106A>T	p.Met36Leu	missense_variant	Exon 1 of 3	3		ENSP00000448819.1	F8VXJ0
ALG10B	ENST00000553138.1 link	n.233A>T		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000127

AC:

AN:

251420

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000237

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000162

AC:

237

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

119

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000132

AC:

AN:

151922

Hom.:

Cov.:

AF XY:

0.0000944

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106A>T (p.M36L) alteration is located in exon 1 (coding exon 1) of the ALG10B gene. This alteration results from a A to T substitution at nucleotide position 106, causing the methionine (M) at amino acid position 36 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.0095

T;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.26

Sift

Benign

0.030

D;T

Sift4G

Benign

0.16

T;T

Polyphen

0.75

P;.

Vest4

0.64

MutPred

0.59

Gain of catalytic residue at E38 (P = 0.0223);Gain of catalytic residue at E38 (P = 0.0223);

MVP

0.38

MPC

0.22

ClinPred

0.19

GERP RS

3.6

Varity_R

0.61

gMVP

0.85

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

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