11-78102951-CAAAAAA-CAAAA

Variant names:

• chr11-78102951-CAA-C
• rs35218171
• NM_024079.5:c.1349+1027_1349+1028delTT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001007027.3(ALG8):​c.1350-5_1350-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 119,654 control chromosomes in the GnomAD database, including 163 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.042 (163 hom., cov: 0)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: ALG8 NM_001007027.3 splice_region, intron
• Clinical Significance: Benign/Likely benign no assertion criteria provided B:2
• 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: Benign. The variant received -9 ACMG points.

• BP6: Variant 11-78102951-CAA-C is Benign according to our data. Variant chr11-78102951-CAA-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1205867.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

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+1027_1349+1028delTT		intron	N/A	NP_076984.2	A0A024R5K5
	ALG8	NM_001425224.1		c.1442+1027_1442+1028delTT		intron	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.1397+1027_1397+1028delTT		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+1027_1349+1028delTT		intron	N/A	ENSP00000299626.5	Q9BVK2-1
	ALG8	ENST00000679559.1		c.1349+1027_1349+1028delTT		intron	N/A	ENSP00000505433.1	A0A7P0T919
	ALG8	ENST00000532440.6	TSL:3	c.1397+1027_1397+1028delTT		intron	N/A	ENSP00000433429.2	H0YDD3

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 4918 AN: 118048 Hom.: 163 Cov.: 0

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.00384

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.0146

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.00410

Gnomad NFE AF: 0.00720

Gnomad OTH AF: 0.0285

GnomAD2 exomes AF: 0.0794 AC: 10 AN: 126 AF XY: 0.0921

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.101 AC: 163 AN: 1618 Hom.: 0 AF XY: 0.0891 AC XY: 96 AN XY: 1078

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

African (AFR) AF: 0.139 AC: 5 AN: 36

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

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 1 AN: 22

East Asian (EAS) AF: 0.0741 AC: 4 AN: 54

South Asian (SAS) AF: 0.112 AC: 11 AN: 98

European-Finnish (FIN) AF: 0.188 AC: 3 AN: 16

Middle Eastern (MID) AF: 0.124 AC: 44 AN: 354

European-Non Finnish (NFE) AF: 0.0908 AC: 79 AN: 870

Other (OTH) AF: 0.135 AC: 14 AN: 104

⚠️ 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: 0.0417 AC: 4918 AN: 118036 Hom.: 163 Cov.: 0 AF XY: 0.0424 AC XY: 2379 AN XY: 56172

African (AFR) AF: 0.105 AC: 3383 AN: 32112

American (AMR) AF: 0.0583 AC: 665 AN: 11416

Ashkenazi Jewish (ASJ) AF: 0.00384 AC: 11 AN: 2868

East Asian (EAS) AF: 0.0677 AC: 280 AN: 4134

South Asian (SAS) AF: 0.0145 AC: 52 AN: 3598

European-Finnish (FIN) AF: 0.0132 AC: 84 AN: 6364

Middle Eastern (MID) AF: 0.00442 AC: 1 AN: 226

European-Non Finnish (NFE) AF: 0.00720 AC: 396 AN: 55004

Other (OTH) AF: 0.0285 AC: 46 AN: 1616

Alfa AF: 0.00466 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13
Mutation Taster		=97/3	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;