rs10502151

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024740.2(ALG9):c.865G>A(p.Val289Ile) variant causes a missense change. The variant allele was found at a frequency of 0.337 in 1,612,176 control chromosomes in the GnomAD database, including 95,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7454 hom., cov: 32)

Exomes 𝑓: 0.34 ( 88153 hom. )

Consequence

ALG9
NM_024740.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 6.17

Publications

41 publications found

Variant links:

Genes affected

ALG9 (HGNC:15672): (ALG9 alpha-1,2-mannosyltransferase) This gene encodes an alpha-1,2-mannosyltransferase enzyme that functions in lipid-linked oligosaccharide assembly. Mutations in this gene result in congenital disorder of glycosylation type Il. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ALG9 Gene-Disease associations (from GenCC):

ALG9-associated autosomal dominant polycystic kidney disease
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
ALG9-congenital disorder of glycosylation
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Orphanet
autosomal dominant polycystic kidney disease
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
Gillessen-Kaesbach-Nishimura syndrome
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ALG9 links:

ENSG00000258529 (HGNC:):

ENSG00000258529 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.7474855E-5).

BP6

Variant 11-111853410-C-T is Benign according to our data. Variant chr11-111853410-C-T is described in ClinVar as [Benign]. Clinvar id is 379945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG9	NM_024740.2 link	c.865G>A	p.Val289Ile	missense_variant	Exon 8 of 15	ENST00000616540.5	NP_079016.2	Q9H6U8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG9	ENST00000616540.5 link	c.865G>A	p.Val289Ile	missense_variant	Exon 8 of 15	1	NM_024740.2	ENSP00000482437.1		Q9H6U8-3
ENSG00000258529	ENST00000622211.4 link	c.1564G>A	p.Val522Ile	missense_variant	Exon 12 of 19	2		ENSP00000482396.1		A0A087WZ62

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44692

AN:

151932

Hom.:

7448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.312

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.586

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.280

GnomAD2 exomes

AF:

0.356

AC:

88629

AN:

248626

AF XY:

0.356

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.270

Gnomad EAS exome

AF:

0.588

Gnomad FIN exome

AF:

0.385

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.334

GnomAD4 exome

AF:

0.342

AC:

499046

AN:

1460124

Hom.:

88153

Cov.:

AF XY:

0.344

AC XY:

249609

AN XY:

726432

show subpopulations

African (AFR)

AF:

0.134

AC:

4498

AN:

33456

American (AMR)

AF:

0.390

AC:

17447

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

6906

AN:

26130

East Asian (EAS)

AF:

0.586

AC:

23239

AN:

39674

South Asian (SAS)

AF:

0.385

AC:

33230

AN:

86210

European-Finnish (FIN)

AF:

0.382

AC:

20410

AN:

53378

Middle Eastern (MID)

AF:

0.346

AC:

1994

AN:

5760

European-Non Finnish (NFE)

AF:

0.334

AC:

371186

AN:

1110476

Other (OTH)

AF:

0.334

AC:

20136

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

16144

32288

48433

64577

80721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.294

AC:

44714

AN:

152052

Hom.:

7454

Cov.:

AF XY:

0.302

AC XY:

22428

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.142

AC:

5891

AN:

41494

American (AMR)

AF:

0.312

AC:

4761

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

892

AN:

3470

East Asian (EAS)

AF:

0.586

AC:

3034

AN:

5178

South Asian (SAS)

AF:

0.392

AC:

1891

AN:

4822

European-Finnish (FIN)

AF:

0.380

AC:

4014

AN:

10554

Middle Eastern (MID)

AF:

0.388

AC:

114

AN:

294

European-Non Finnish (NFE)

AF:

0.339

AC:

23020

AN:

67954

Other (OTH)

AF:

0.283

AC:

595

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1534

3069

4603

6138

7672

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.322

Hom.:

26072

Bravo

AF:

0.285

TwinsUK

AF:

0.326

AC:

1210

ALSPAC

AF:

0.336

AC:

1294

ESP6500AA

AF:

0.136

AC:

516

ESP6500EA

AF:

0.322

AC:

2653

ExAC

AF:

0.350

AC:

42265

Asia WGS

AF:

0.430

AC:

1495

AN:

3478

EpiCase

AF:

0.322

EpiControl

AF:

0.327

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

ALG9 congenital disorder of glycosylation

Benign:3

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Gillessen-Kaesbach-Nishimura syndrome

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 02, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;.;.;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

T;T;T;T;T

MetaRNN

Benign

0.000097

T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.1

L;.;.;L;.

PhyloP100

6.2

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.69

.;N;N;.;.

REVEL

Benign

0.22

Sift

Benign

0.17

.;T;T;.;.

Sift4G

Benign

0.13

T;T;T;T;T

Polyphen

0.97

D;.;.;D;.

Vest4

0.15

MPC

0.30

ClinPred

0.023

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.76

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

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rs10502151

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over