11-111783917-GTTT-GT

Variant names:

• chr11-111783917-GTT-G
• rs376955296
• NM_024740.2:c.*2478_*2479delAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_024740.2(ALG9):​c.*2478_*2479delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00527 in 116,234 control chromosomes in the GnomAD database, including 6 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0053 (6 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: ALG9 NM_024740.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• 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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00527 (613/116234) while in subpopulation AFR AF = 0.0156 (495/31760). AF 95% confidence interval is 0.0145. There are 6 homozygotes in GnomAd4. There are 294 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR,AD gene

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.*2478_*2479delAA		3_prime_UTR	Exon 15 of 15	NP_079016.2	Q9H6U8-3
	ALG9	NM_001441203.1		c.*2138_*2139delAA		3_prime_UTR	Exon 16 of 16	NP_001428132.1
	ALG9	NM_001352417.1		c.*2138_*2139delAA		3_prime_UTR	Exon 16 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.*2478_*2479delAA		3_prime_UTR	Exon 15 of 15	ENSP00000482437.1	Q9H6U8-3
	ALG9	ENST00000532425.6	TSL:3	c.*2138_*2139delAA		3_prime_UTR	Exon 6 of 6	ENSP00000432442.2	H0YCW6

Frequencies

GnomAD3 genomes AF: 0.00526 AC: 611 AN: 116172 Hom.: 6 Cov.: 29

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00191

Gnomad ASJ AF: 0.00112

Gnomad EAS AF: 0.00522

Gnomad SAS AF: 0.000815

Gnomad FIN AF: 0.000468

Gnomad MID AF: 0.00855

Gnomad NFE AF: 0.00108

Gnomad OTH AF: 0.00458

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

GnomAD4 genome AF: 0.00527 AC: 613 AN: 116234 Hom.: 6 Cov.: 29 AF XY: 0.00529 AC XY: 294 AN XY: 55540

African (AFR) AF: 0.0156 AC: 495 AN: 31760

American (AMR) AF: 0.00190 AC: 20 AN: 10502

Ashkenazi Jewish (ASJ) AF: 0.00112 AC: 3 AN: 2688

East Asian (EAS) AF: 0.00524 AC: 22 AN: 4200

South Asian (SAS) AF: 0.000544 AC: 2 AN: 3676

European-Finnish (FIN) AF: 0.000468 AC: 3 AN: 6414

Middle Eastern (MID) AF: 0.00926 AC: 2 AN: 216

European-Non Finnish (NFE) AF: 0.00108 AC: 59 AN: 54428

Other (OTH) AF: 0.00453 AC: 7 AN: 1544

Alfa AF: 0.000380 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs376955296; hg19: chr11-111654641;