chr11-111857609-C-T

Variant names:

• chr11-111857609-C-T
• rs36111204
• NM_024740.2:c.694G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024740.2(ALG9):​c.694G>A​(p.Ala232Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A232P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ALG9 NM_024740.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61
• Publications: 4 publications found

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: G2P, Ambry Genetics, Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• Gillessen-Kaesbach-Nishimura syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000258529 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024740.2. 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
	ALG9	NM_024740.2	MANE Select	c.694G>A	p.Ala232Thr	missense	Exon 6 of 15	NP_079016.2	Q9H6U8-3
	ALG9	NM_001441203.1		c.694G>A	p.Ala232Thr	missense	Exon 6 of 16	NP_001428132.1
	ALG9	NM_001352417.1		c.694G>A	p.Ala232Thr	missense	Exon 6 of 16	NP_001339346.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG9	ENST00000616540.5	TSL:1 MANE Select	c.694G>A	p.Ala232Thr	missense	Exon 6 of 15	ENSP00000482437.1	Q9H6U8-3
	ENSG00000258529	ENST00000622211.4	TSL:2	c.1393G>A	p.Ala465Thr	missense	Exon 10 of 19	ENSP00000482396.1	A0A087WZ62
	ALG9	ENST00000614444.4	TSL:1	c.694G>A	p.Ala232Thr	missense	Exon 6 of 15	ENSP00000484200.1	Q9H6U8-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461844 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727230

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.27
Sift	Benign	0.16	T
Sift4G	Benign	0.25	T
Polyphen		0.76	P
Vest4		0.67
MutPred		0.46		Loss of helix (P = 0.1299)
MVP		0.87
MPC		0.54
ClinPred		0.63	D
GERP RS		6.0
Varity_R		0.24
gMVP		0.58
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs36111204; hg19: chr11-111728332;