rs518624

Variant names:

• chr11-78121030-T-A
• rs518624
• NM_024079.5:c.478+35A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-78121030-T-A
• chr11-78121030-T-C

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.478+35A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 152,304 control chromosomes in the GnomAD database, including 76,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (76149 hom., cov: 31)
  • Exomes 𝑓: 1.0 (670938 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALG8 NM_024079.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.671
• 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=-0.83).
• BP6: Variant 11-78121030-T-A is Benign according to our data. Variant chr11-78121030-T-A is described in ClinVar as Benign. ClinVar VariationId is 261680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.994 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.478+35A>T		intron	N/A	NP_076984.2
	ALG8	NM_001425224.1		c.478+35A>T		intron	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.478+35A>T		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.478+35A>T		intron	N/A	ENSP00000299626.5
	ALG8	ENST00000532050.5	TSL:1	n.478+35A>T		intron	N/A	ENSP00000437199.1
	ALG8	ENST00000680650.1		n.419A>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 1.00 AC: 152183 AN: 152186 Hom.: 76090 Cov.: 31

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD2 exomes AF: 1.00 AC: 250450 AN: 250450 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 1.00 AC: 1341878 AN: 1341880 Hom.: 670938 Cov.: 20 AF XY: 1.00 AC XY: 674517 AN XY: 674518

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

African (AFR) AF: 1.00 AC: 31038 AN: 31038

American (AMR) AF: 1.00 AC: 44588 AN: 44588

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 25430 AN: 25430

East Asian (EAS) AF: 1.00 AC: 39026 AN: 39026

South Asian (SAS) AF: 1.00 AC: 83790 AN: 83790

European-Finnish (FIN) AF: 1.00 AC: 52669 AN: 52670

Middle Eastern (MID) AF: 1.00 AC: 5526 AN: 5526

European-Non Finnish (NFE) AF: 1.00 AC: 1003331 AN: 1003332

Other (OTH) AF: 1.00 AC: 56480 AN: 56480

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 1.00 AC: 152301 AN: 152304 Hom.: 76149 Cov.: 31 AF XY: 1.00 AC XY: 74472 AN XY: 74474

African (AFR) AF: 1.00 AC: 41550 AN: 41552

American (AMR) AF: 1.00 AC: 15288 AN: 15288

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5178

South Asian (SAS) AF: 1.00 AC: 4823 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10624 AN: 10624

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68044 AN: 68044

Other (OTH) AF: 1.00 AC: 2116 AN: 2116

Alfa AF: 1.00 Hom.: 13791

Bravo AF: 1.00

Asia WGS AF: 1.00 AC: 3478 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	ALG8 congenital disorder of glycosylation (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.80
PhyloP100		0.67
Mutation Taster		=100/0	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: rs518624; hg19: chr11-77832076;