chr1-63367765-C-G

Position:

• chr1-63367765-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.-208+78C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 152,354 control chromosomes in the GnomAD database, including 827 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (827 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: ALG6 NM_013339.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25

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=-0.75).
• BP6: Variant 1-63367765-C-G is Benign according to our data. Variant chr1-63367765-C-G is described in ClinVar as [Benign]. Clinvar id is 1230123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG6	NM_013339.4	c.-208+78C>G		intron_variant		ENST00000263440.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG6	ENST00000263440.6	c.-208+78C>G		intron_variant		5	NM_013339.4	P1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 15087 AN: 152096 Hom.: 823 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0779

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0955

GnomAD4 exome AF: 0.129 AC: 18 AN: 140 Hom.: 0 AF XY: 0.140 AC XY: 14 AN XY: 100

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0993 AC: 15120 AN: 152214 Hom.: 827 Cov.: 32 AF XY: 0.0989 AC XY: 7363 AN XY: 74432

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.0639

Gnomad4 NFE AF: 0.0857

Gnomad4 OTH AF: 0.0978

Alfa AF: 0.0425 Hom.: 40

Bravo AF: 0.0992

Asia WGS AF: 0.175 AC: 608 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 12, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.1
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: rs3737897; hg19: chr1-63833436;