chr1-63367903-G-T

Variant names:

• chr1-63367903-G-T
• rs75502742
• NM_013339.4:c.-208+216G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013339.4(ALG6):​c.-208+216G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 152,310 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.024 (117 hom., cov: 32)
• Consequence: ALG6 NM_013339.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.570
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-63367903-G-T is Benign according to our data. Variant chr1-63367903-G-T is described in ClinVar as Benign. ClinVar VariationId is 1242754.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0756 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.-208+216G>T		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.-208+216G>T		intron	N/A	ENSP00000263440.5	Q9Y672
	ALG6	ENST00000948329.1		c.-208+221G>T		intron	N/A	ENSP00000618388.1
	ALG6	ENST00000920026.1		c.-208+216G>T		intron	N/A	ENSP00000590085.1

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3680 AN: 152192 Hom.: 113 Cov.: 32

Gnomad AFR AF: 0.0775

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0229

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

GnomAD4 genome AF: 0.0243 AC: 3702 AN: 152310 Hom.: 117 Cov.: 32 AF XY: 0.0244 AC XY: 1817 AN XY: 74490

African (AFR) AF: 0.0778 AC: 3235 AN: 41560

American (AMR) AF: 0.00653 AC: 100 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0178 AC: 92 AN: 5174

South Asian (SAS) AF: 0.0186 AC: 90 AN: 4834

European-Finnish (FIN) AF: 0.0106 AC: 113 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68026

Other (OTH) AF: 0.0227 AC: 48 AN: 2114

Alfa AF: 0.0164 Hom.: 13

Bravo AF: 0.0255

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.6
DANN	Benign	0.80
PhyloP100		0.57
PromoterAI		0.021	Neutral
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: rs75502742; hg19: chr1-63833574;