rs45574638

Positions:

chr11-111865258-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_024740.2(ALG9):c.406-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 1,548,022 control chromosomes in the GnomAD database, including 906 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 78 hom., cov: 33)

Exomes 𝑓: 0.033 ( 828 hom. )

Consequence

ALG9
NM_024740.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006998

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.852

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 11-111865258-G-A is Benign according to our data. Variant chr11-111865258-G-A is described in ClinVar as [Benign]. Clinvar id is 96134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0252 (3831/152152) while in subpopulation NFE AF= 0.0362 (2461/67974). AF 95% confidence interval is 0.035. There are 78 homozygotes in gnomad4. There are 1894 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 78 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG9	NM_024740.2 linkuse as main transcript	c.406-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000616540.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG9	ENST00000616540.5 linkuse as main transcript	c.406-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_024740.2		Q9H6U8-3

Frequencies

GnomAD3 genomes

AF:

0.0252

AC:

3830

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00602

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0336

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.0399

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0362

Gnomad OTH

AF:

0.0340

GnomAD3 exomes

AF:

0.0251

AC:

3942

AN:

157232

Hom.:

AF XY:

0.0253

AC XY:

2095

AN XY:

82680

show subpopulations

Gnomad AFR exome

AF:

0.00468

Gnomad AMR exome

AF:

0.0208

Gnomad ASJ exome

AF:

0.0244

Gnomad EAS exome

AF:

0.000185

Gnomad SAS exome

AF:

0.00937

Gnomad FIN exome

AF:

0.0351

Gnomad NFE exome

AF:

0.0367

Gnomad OTH exome

AF:

0.0263

GnomAD4 exome

AF:

0.0326

AC:

45528

AN:

1395870

Hom.:

828

Cov.:

AF XY:

0.0319

AC XY:

21974

AN XY:

688562

show subpopulations

Gnomad4 AFR exome

AF:

0.00520

Gnomad4 AMR exome

AF:

0.0215

Gnomad4 ASJ exome

AF:

0.0255

Gnomad4 EAS exome

AF:

0.0000841

Gnomad4 SAS exome

AF:

0.0111

Gnomad4 FIN exome

AF:

0.0323

Gnomad4 NFE exome

AF:

0.0369

Gnomad4 OTH exome

AF:

0.0291

GnomAD4 genome

AF:

0.0252

AC:

3831

AN:

152152

Hom.:

Cov.:

AF XY:

0.0255

AC XY:

1894

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00600

Gnomad4 AMR

AF:

0.0335

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00849

Gnomad4 FIN

AF:

0.0399

Gnomad4 NFE

AF:

0.0362

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0318

Hom.:

Bravo

AF:

0.0242

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 29, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2016	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. -

ALG9 congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

8.1

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000070

dbscSNV1_RF

Benign

0.040

SpliceAI score (max)

0.030

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