11-111853408-GAC-TAT

Variant names:

• chr11-111853408-GAC-TAT
• NM_024740.2:c.865_867delGTCinsATA
• ALG9 p.Val289Ile

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_024740.2(ALG9):​c.865_867delGTCinsATA​(p.Val289Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALG9 NM_024740.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 0 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, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.865_867delGTCinsATA	p.Val289Ile	missense	N/A	NP_079016.2	Q9H6U8-3
	ALG9	NM_001441203.1		c.865_867delGTCinsATA	p.Val289Ile	missense	N/A	NP_001428132.1
	ALG9	NM_001352417.1		c.865_867delGTCinsATA	p.Val289Ile	missense	N/A	NP_001339346.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG9	ENST00000616540.5	TSL:1 MANE Select	c.865_867delGTCinsATA	p.Val289Ile	missense	N/A	ENSP00000482437.1	Q9H6U8-3
	ENSG00000258529	ENST00000622211.4	TSL:2	c.1564_1566delGTCinsATA	p.Val522Ile	missense	N/A	ENSP00000482396.1	A0A087WZ62
	ALG9	ENST00000614444.4	TSL:1	c.865_867delGTCinsATA	p.Val289Ile	missense	N/A	ENSP00000484200.1	Q9H6U8-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-111724131;