chr1-63367779-G-T

Position:

• chr1-63367779-G-T

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.-208+92G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 152,412 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (507 hom., cov: 32)
  • Exomes 𝑓: 0.075 (0 hom.)
• Consequence: ALG6 NM_013339.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.932

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=-0.74).
• BP6: Variant 1-63367779-G-T is Benign according to our data. Variant chr1-63367779-G-T is described in ClinVar as [Benign]. Clinvar id is 1269353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG6	NM_013339.4	c.-208+92G>T		intron_variant		ENST00000263440.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG6	ENST00000263440.6	c.-208+92G>T		intron_variant		5	NM_013339.4	P1

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 10798 AN: 152160 Hom.: 506 Cov.: 32

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0851

Gnomad OTH AF: 0.0679

GnomAD4 exome AF: 0.0746 AC: 10 AN: 134 Hom.: 0 AF XY: 0.0816 AC XY: 8 AN XY: 98

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0847

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0710 AC: 10805 AN: 152278 Hom.: 507 Cov.: 32 AF XY: 0.0706 AC XY: 5256 AN XY: 74458

Gnomad4 AFR AF: 0.0335

Gnomad4 AMR AF: 0.0687

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.0851

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0758 Hom.: 61

Bravo AF: 0.0693

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 12, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.79

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: rs3737898; hg19: chr1-63833450;