11-111853410-C-T

Position:

chr11-111853410-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 links:

ENSG00000258529 (HGNC:):

ENSG00000258529 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr11-111853410-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ALG9	NM_024740.2 linkuse as main transcript	c.865G>A	p.Val289Ile	missense_variant	8/15	ENST00000616540.5	NP_079016.2	Q9H6U8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG9	ENST00000616540.5 linkuse as main transcript	c.865G>A	p.Val289Ile	missense_variant	8/15	1	NM_024740.2	ENSP00000482437.1		Q9H6U8-3
ENSG00000258529	ENST00000622211.4 linkuse as main transcript	c.1564G>A	p.Val522Ile	missense_variant	12/19	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

GnomAD3 exomes

AF:

0.356

AC:

88629

AN:

248626

Hom.:

16822

AF XY:

0.356

AC XY:

48083

AN XY:

134908

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 SAS exome

AF:

0.388

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

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.390

Gnomad4 ASJ exome

AF:

0.264

Gnomad4 EAS exome

AF:

0.586

Gnomad4 SAS exome

AF:

0.385

Gnomad4 FIN exome

AF:

0.382

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.334

GnomAD4 genome

AF:

0.294

AC:

44714

AN:

152052

Hom.:

7454

Cov.:

AF XY:

0.302

AC XY:

22428

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.312

Gnomad4 ASJ

AF:

0.257

Gnomad4 EAS

AF:

0.586

Gnomad4 SAS

AF:

0.392

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.339

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.331

Hom.:

19261

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2015

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. -

Gillessen-Kaesbach-Nishimura syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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;.

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

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