Genetic Variant ALG10B:p.Ser25Phe (chr12-38316967-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is . The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001013620.4(ALG10B):c.74C>T(p.Ser25Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S25C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ALG10B
NM_001013620.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.04

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

long QT syndrome
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
long QT syndrome 2
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ALG10B links:

ENSG00000301992 (HGNC:):

ENSG00000301992 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001013620.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.192).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013620.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG10B	NM_001013620.4	MANE Select	c.74C>T	p.Ser25Phe	missense	Exon 1 of 3	NP_001013642.2	Q5I7T1
	ALG10B	NM_001308340.2		c.74C>T	p.Ser25Phe	missense	Exon 1 of 3	NP_001295269.2	F8VXJ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG10B	ENST00000308742.9	TSL:1 MANE Select	c.74C>T	p.Ser25Phe	missense	Exon 1 of 3	ENSP00000310120.4	Q5I7T1
ALG10B	ENST00000548240.1	TSL:1	n.74C>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000449210.1	F8VWA9
ALG10B	ENST00000551464.1	TSL:3	c.74C>T	p.Ser25Phe	missense	Exon 1 of 3	ENSP00000448819.1	F8VXJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0056

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.010

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

5.0

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.7

REVEL

Benign

0.19

Sift

Uncertain

0.020

Sift4G

Benign

0.15

PromoterAI

0.058

Neutral

(source)

Varity_R

0.22

gMVP

0.79

Mutation Taster

=49/51

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over