rs3004318

Variant names:

• chr1-63435068-G-A
• rs3004318
• NM_013339.4:c.1327-1755G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013339.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG6	NM_013339.4	MANE Select	c.1327-1755G>A		intron	N/A	NP_037471.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG6	ENST00000263440.6	TSL:5 MANE Select	c.1327-1755G>A		intron	N/A	ENSP00000263440.5	Q9Y672
	ALG6	ENST00000948329.1		c.1327-1755G>A		intron	N/A	ENSP00000618388.1
	ALG6	ENST00000920026.1		c.1312-1755G>A		intron	N/A	ENSP00000590085.1

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

African (AFR) AF: 0.819 AC: 34002 AN: 41494

American (AMR) AF: 0.653 AC: 9971 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2072 AN: 3468

East Asian (EAS) AF: 0.675 AC: 3485 AN: 5164

South Asian (SAS) AF: 0.644 AC: 3099 AN: 4814

European-Finnish (FIN) AF: 0.434 AC: 4579 AN: 10556

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32920 AN: 67946

Other (OTH) AF: 0.609 AC: 1281 AN: 2104

Alfa AF: 0.542 Hom.: 15617

Bravo AF: 0.632

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.36
PhyloP100		-1.1
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: rs3004318; hg19: chr1-63900739; COSMIC: COSV107216751;