Variant rs387906925 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_019109.5(ALG1):c.1129A>G(p.Met377Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,611,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ALG1
NM_019109.5 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.14

Variant links:

Genes affected

ALG1 (HGNC:18294): (ALG1 chitobiosyldiphosphodolichol beta-mannosyltransferase) The enzyme encoded by this gene catalyzes the first mannosylation step in the biosynthesis of lipid-linked oligosaccharides. This gene is mutated in congenital disorder of glycosylation type Ik. [provided by RefSeq, Dec 2008]

ALG1 links:

ALG1 (HGNC:):

ALG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.937

PP5

Variant 16-5082615-A-G is Pathogenic according to our data. Variant chr16-5082615-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 30536.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG1	NM_019109.5 linkuse as main transcript	c.1129A>G	p.Met377Val	missense_variant	11/13	ENST00000262374.10	NP_061982.3	Q9BT22-1
ALG1	NM_001330504.2 linkuse as main transcript	c.796A>G	p.Met266Val	missense_variant	11/13		NP_001317433.1	Q9BT22-2
ALG1	XM_017023457.3 linkuse as main transcript	c.1090A>G	p.Met364Val	missense_variant	10/12		XP_016878946.1	A0A804HJL6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG1	ENST00000262374.10 linkuse as main transcript	c.1129A>G	p.Met377Val	missense_variant	11/13	1	NM_019109.5	ENSP00000262374.5		Q9BT22-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250572

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459694

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726154

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ALG1-congenital disorder of glycosylation

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

.;D;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

.;T;D

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Uncertain

0.54

MutationAssessor

Pathogenic

4.0

.;H;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.8

.;D;D

REVEL

Pathogenic

0.88

Sift

Pathogenic

0.0

.;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.95

.;P;.

Vest4

0.87

MutPred

0.79

.;Gain of methylation at K378 (P = 0.0282);.;

MVP

0.89

MPC

2.3

ClinPred

1.0

GERP RS

5.3

Varity_R

0.93

gMVP

0.80

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