Genetic Variant ALG1L2:p.His124Asn (chr3-130094459-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001136152.1(ALG1L2):c.370C>A(p.His124Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,444,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict 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. H124Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

ALG1L2
NM_001136152.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.58

Publications

0 publications found

Variant links:

Genes affected

ALG1L2 (HGNC:37258): (ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase like 2) Predicted to enable mannosyltransferase activity. Predicted to be involved in protein glycosylation. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ALG1L2 links:

LINC02014 (HGNC:52849): (long intergenic non-protein coding RNA 2014)

LINC02014 links:

ENSG00000291081 (HGNC:):

ENSG00000291081 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1141963).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136152.1. 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
	ALG1L2	NM_001136152.1	MANE Select	c.370C>A	p.His124Asn	missense	Exon 5 of 8	NP_001129624.1	C9J202
	LINC02014	NR_146710.1		n.-155G>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG1L2	ENST00000425059.1	TSL:5 MANE Select	c.370C>A	p.His124Asn	missense	Exon 5 of 8	ENSP00000479850.1	C9J202
ALG1L2	ENST00000698236.2		c.409C>A	p.His137Asn	missense	Exon 6 of 9	ENSP00000513618.2	A0A8V8TNA5
ALG1L2	ENST00000698237.1		c.370C>A	p.His124Asn	missense	Exon 5 of 8	ENSP00000513619.1	A0A8V8TLI2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000430

AC:

AN:

232720

AF XY:

0.00000780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000923

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1444028

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718762

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4144

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111658

Other (OTH)

AF:

0.00

AC:

AN:

60104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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.:

Alfa

AF:

0.0000480

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.11

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.53

MetaRNN

Benign

0.11

MutationAssessor

Benign

0.88

PhyloP100

1.6

PrimateAI

Uncertain

0.61

Sift4G

Benign

0.29

Polyphen

0.0060

Vest4

0.20

MVP

0.15

GERP RS

1.2

Varity_R

0.049

gMVP

0.56

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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