1-63393375-C-T

Variant names:

• chr1-63393375-C-T
• rs10789138
• NM_013339.4:c.83-3138C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013339.4(ALG6):​c.83-3138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,150 control chromosomes in the GnomAD database, including 44,287 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 0.76 (44287 hom., cov: 33)
• Consequence: ALG6 NM_013339.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573
• Publications: 14 publications found

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]

ITGB3BP (HGNC:6157): (integrin subunit beta 3 binding protein) This gene encodes a transcriptional coregulator that binds to and enhances the activity of members of the nuclear receptor families, thyroid hormone receptors and retinoid X receptors. This protein also acts as a corepressor of NF-kappaB-dependent signaling. This protein induces apoptosis in breast cancer cells through a caspase 2-mediated signaling pathway. This protein is also a component of the centromere-specific histone H3 variant nucleosome associated complex (CENP-NAC) and may be involved in mitotic progression by recruiting the histone H3 variant CENP-A to the centromere. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG6	NM_013339.4	c.83-3138C>T		intron_variant	Intron 2 of 14	ENST00000263440.6	NP_037471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG6	ENST00000263440.6	c.83-3138C>T		intron_variant	Intron 2 of 14	5	NM_013339.4	ENSP00000263440.5

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115201 AN: 152032 Hom.: 44235 Cov.: 33

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.758 AC: 115309 AN: 152150 Hom.: 44287 Cov.: 33 AF XY: 0.759 AC XY: 56464 AN XY: 74378

African (AFR) AF: 0.868 AC: 36060 AN: 41536

American (AMR) AF: 0.765 AC: 11692 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2697 AN: 3468

East Asian (EAS) AF: 0.858 AC: 4447 AN: 5182

South Asian (SAS) AF: 0.864 AC: 4168 AN: 4826

European-Finnish (FIN) AF: 0.682 AC: 7204 AN: 10562

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46542 AN: 67976

Other (OTH) AF: 0.768 AC: 1621 AN: 2112

Alfa AF: 0.727 Hom.: 7757

Bravo AF: 0.769

Asia WGS AF: 0.851 AC: 2956 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.54
DANN	Benign	0.49
PhyloP100		-0.57
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: rs10789138; hg19: chr1-63859046;