chr11-78102951-CA-C

Variant names:

• chr11-78102951-CA-C
• rs35218171
• NM_024079.5:c.1349+1028delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001007027.3(ALG8):​c.1350-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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 0.62 (19500 hom., cov: 0)
  • Exomes 𝑓: 0.39 (21 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 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+1028delT		intron	N/A	NP_076984.2	A0A024R5K5
	ALG8	NM_001425224.1		c.1442+1028delT		intron	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.1397+1028delT		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+1028delT		intron	N/A	ENSP00000299626.5	Q9BVK2-1
	ALG8	ENST00000679559.1		c.1349+1028delT		intron	N/A	ENSP00000505433.1	A0A7P0T919
	ALG8	ENST00000532440.6	TSL:3	c.1397+1028delT		intron	N/A	ENSP00000433429.2	H0YDD3

Frequencies

GnomAD3 genomes AF: 0.618 AC: 73016 AN: 118074 Hom.: 19508 Cov.: 0

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.619

GnomAD2 exomes AF: 0.397 AC: 50 AN: 126 AF XY: 0.382

Gnomad AFR exome AF: 0.500

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.500

Gnomad NFE exome AF: 0.383

Gnomad OTH exome AF: 0.333

GnomAD4 exome AF: 0.388 AC: 629 AN: 1622 Hom.: 21 Cov.: 0 AF XY: 0.388 AC XY: 420 AN XY: 1082

African (AFR) AF: 0.417 AC: 15 AN: 36

American (AMR) AF: 0.367 AC: 22 AN: 60

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 10 AN: 24

East Asian (EAS) AF: 0.333 AC: 18 AN: 54

South Asian (SAS) AF: 0.316 AC: 31 AN: 98

European-Finnish (FIN) AF: 0.125 AC: 2 AN: 16

Middle Eastern (MID) AF: 0.494 AC: 175 AN: 354

European-Non Finnish (NFE) AF: 0.366 AC: 320 AN: 874

Other (OTH) AF: 0.340 AC: 36 AN: 106

GnomAD4 genome AF: 0.618 AC: 73005 AN: 118062 Hom.: 19500 Cov.: 0 AF XY: 0.615 AC XY: 34584 AN XY: 56196

African (AFR) AF: 0.676 AC: 21708 AN: 32104

American (AMR) AF: 0.502 AC: 5731 AN: 11420

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 1692 AN: 2868

East Asian (EAS) AF: 0.580 AC: 2398 AN: 4134

South Asian (SAS) AF: 0.613 AC: 2205 AN: 3600

European-Finnish (FIN) AF: 0.623 AC: 3981 AN: 6394

Middle Eastern (MID) AF: 0.628 AC: 142 AN: 226

European-Non Finnish (NFE) AF: 0.614 AC: 33757 AN: 55006

Other (OTH) AF: 0.620 AC: 999 AN: 1612

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		=99/1	polymorphism (auto)

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; COSMIC: COSV107347775; COSMIC: COSV107347775;