11-78109624-T-C

Variant names:

• chr11-78109624-T-C
• rs1783515
• NM_024079.5:c.899-43A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024079.5(ALG8):​c.899-43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,536,924 control chromosomes in the GnomAD database, including 26,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4395 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22090 hom.)
• Consequence: ALG8 NM_024079.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.261
• Publications: 6 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):

• ALG8-congenital disorder of glycosylation

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

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-78109624-T-C is Benign according to our data. Variant chr11-78109624-T-C is described in ClinVar as Benign. ClinVar VariationId is 261683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024079.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	NM_024079.5	MANE Select	c.899-43A>G		intron	N/A	NP_076984.2
	ALG8	NM_001425224.1		c.992-43A>G		intron	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.899-43A>G		intron	N/A	NP_001412154.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000299626.10	TSL:1 MANE Select	c.899-43A>G		intron	N/A	ENSP00000299626.5
	ALG8	ENST00000679559.1		c.899-43A>G		intron	N/A	ENSP00000505433.1
	ALG8	ENST00000532440.6	TSL:3	c.899-43A>G		intron	N/A	ENSP00000433429.2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33048 AN: 151832 Hom.: 4392 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.203

GnomAD2 exomes AF: 0.181 AC: 43439 AN: 240636 AF XY: 0.180

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.0937

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.301

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.172 AC: 237733 AN: 1384976 Hom.: 22090 Cov.: 24 AF XY: 0.172 AC XY: 118929 AN XY: 693092

African (AFR) AF: 0.397 AC: 12661 AN: 31906

American (AMR) AF: 0.0980 AC: 4338 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3955 AN: 25622

East Asian (EAS) AF: 0.300 AC: 11667 AN: 38952

South Asian (SAS) AF: 0.214 AC: 17999 AN: 84190

European-Finnish (FIN) AF: 0.115 AC: 6080 AN: 52932

Middle Eastern (MID) AF: 0.247 AC: 1386 AN: 5618

European-Non Finnish (NFE) AF: 0.162 AC: 168668 AN: 1043582

Other (OTH) AF: 0.190 AC: 10979 AN: 57890

GnomAD4 genome AF: 0.218 AC: 33071 AN: 151948 Hom.: 4395 Cov.: 32 AF XY: 0.212 AC XY: 15780 AN XY: 74282

African (AFR) AF: 0.379 AC: 15664 AN: 41320

American (AMR) AF: 0.130 AC: 1991 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3468

East Asian (EAS) AF: 0.284 AC: 1464 AN: 5160

South Asian (SAS) AF: 0.201 AC: 968 AN: 4812

European-Finnish (FIN) AF: 0.0976 AC: 1035 AN: 10602

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10754 AN: 67972

Other (OTH) AF: 0.201 AC: 424 AN: 2112

Alfa AF: 0.192 Hom.: 627

Bravo AF: 0.229

Asia WGS AF: 0.226 AC: 786 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.59
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1783515; hg19: chr11-77820670;