rs3004318

Positions:

• chr1-63435068-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013339.4(ALG6):​c.1327-1755G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,012 control chromosomes in the GnomAD database, including 29,622 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (29622 hom., cov: 31)
• Consequence: ALG6 NM_013339.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG6	NM_013339.4	c.1327-1755G>A		intron_variant		ENST00000263440.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG6	ENST00000263440.6	c.1327-1755G>A		intron_variant		5	NM_013339.4	P1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91935 AN: 151894 Hom.: 29574 Cov.: 31

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.608

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.605 AC: 92036 AN: 152012 Hom.: 29622 Cov.: 31 AF XY: 0.604 AC XY: 44863 AN XY: 74300

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.609

Alfa AF: 0.529 Hom.: 9980

Bravo AF: 0.632

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.36

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: rs3004318; hg19: chr1-63900739;