1-63370842-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013339.4(ALG6):c.-136C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 714,454 control chromosomes in the GnomAD database, including 14,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3157 hom., cov: 32)
  • Exomes 𝑓: 0.19 (11127 hom.)
• Consequence: ALG6 NM_013339.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0690

Genes affected

ALG6 (HGNC:23157): (ALG6 alpha-1,3-glucosyltransferase) This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the first glucose residue to the growing lipid-linked oligosaccharide precursor of N-linked glycosylation. Mutations in this gene are associated with congenital disorders of glycosylation type Ic. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-63370842-C-G is Benign according to our data. Variant chr1-63370842-C-G is described in ClinVar as [Benign]. Clinvar id is 297843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG6	NM_013339.4	c.-136C>G		5_prime_UTR_variant	2/15	ENST00000263440.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG6	ENST00000263440.6	c.-136C>G		5_prime_UTR_variant	2/15	5	NM_013339.4	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30456 AN: 151798 Hom.: 3152 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.195 AC: 109427 AN: 562538 Hom.: 11127 Cov.: 6 AF XY: 0.195 AC XY: 59531 AN XY: 304740

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.307

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.201 AC: 30489 AN: 151916 Hom.: 3157 Cov.: 32 AF XY: 0.198 AC XY: 14700 AN XY: 74252

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.217

Alfa AF: 0.187 Hom.: 376

Bravo AF: 0.208

Asia WGS AF: 0.183 AC: 633 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

ALG6-congenital disorder of glycosylation 1C Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	4.4
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs34542411; hg19: chr1-63836513; COSMIC: COSV54763906;