11-78102951-CAAAAAA-CAAA

Variant names:

• chr11-78102951-CAAA-C
• rs35218171
• NM_024079.5:c.1349+1026_1349+1028delTTT

Variant summary

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

The NM_001007027.3(ALG8):​c.1350-6_1350-4delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000426 in 119,618 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: ALG8 NM_001007027.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 0 publications found

Genes affected

ALG8 (HGNC:23161): (ALG8 alpha-1,3-glucosyltransferase) This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins. Mutations in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ih). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ALG8 Gene-Disease associations (from GenCC):

• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• ALG8-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• polycystic liver disease 3 with or without kidney cysts

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007027.3. 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
	ALG8	NM_024079.5	MANE Select	c.1349+1026_1349+1028delTTT		intron	N/A	NP_076984.2	A0A024R5K5
	ALG8	NM_001425224.1		c.1442+1026_1442+1028delTTT		intron	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.1397+1026_1397+1028delTTT		intron	N/A	NP_001412154.1	H0YDD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000299626.10	TSL:1 MANE Select	c.1349+1026_1349+1028delTTT		intron	N/A	ENSP00000299626.5	Q9BVK2-1
	ALG8	ENST00000679559.1		c.1349+1026_1349+1028delTTT		intron	N/A	ENSP00000505433.1	A0A7P0T919
	ALG8	ENST00000532440.6	TSL:3	c.1397+1026_1397+1028delTTT		intron	N/A	ENSP00000433429.2	H0YDD3

Frequencies

GnomAD3 genomes AF: 0.000153 AC: 18 AN: 118030 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000351

Gnomad ASJ AF: 0.000349

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000314

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000109

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0238 AC: 3 AN: 126 AF XY: 0.0263

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0588

Gnomad ASJ exome AF: 0.00

Gnomad NFE exome AF: 0.0167

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0206 AC: 33 AN: 1600 Hom.: 0 AF XY: 0.0207 AC XY: 22 AN XY: 1064

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 36

American (AMR) AF: 0.0313 AC: 2 AN: 64

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24

East Asian (EAS) AF: 0.0192 AC: 1 AN: 52

South Asian (SAS) AF: 0.0306 AC: 3 AN: 98

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16

Middle Eastern (MID) AF: 0.00565 AC: 2 AN: 354

European-Non Finnish (NFE) AF: 0.0257 AC: 22 AN: 856

Other (OTH) AF: 0.0300 AC: 3 AN: 100

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000153 AC: 18 AN: 118018 Hom.: 0 Cov.: 0 AF XY: 0.000214 AC XY: 12 AN XY: 56174

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000156 AC: 5 AN: 32082

American (AMR) AF: 0.000350 AC: 4 AN: 11420

Ashkenazi Jewish (ASJ) AF: 0.000349 AC: 1 AN: 2868

East Asian (EAS) AF: 0.00 AC: 0 AN: 4134

South Asian (SAS) AF: 0.00 AC: 0 AN: 3598

European-Finnish (FIN) AF: 0.000314 AC: 2 AN: 6368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.000109 AC: 6 AN: 55010

Other (OTH) AF: 0.00 AC: 0 AN: 1614

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000001541), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13
Mutation Taster		=98/2	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: rs35218171; hg19: chr11-77813997;