chr1-63367779-G-T

Variant names:

• chr1-63367779-G-T
• rs3737898
• NM_013339.4:c.-208+92G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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]

ENSG00000300378 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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+92G>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+92G>T		intron	N/A	ENSP00000263440.5	Q9Y672
	ALG6	ENST00000948329.1		c.-208+97G>T		intron	N/A	ENSP00000618388.1
	ALG6	ENST00000920026.1		c.-208+92G>T		intron	N/A	ENSP00000590085.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0847 AC: 10 AN: 118

Other (OTH) AF: 0.00 AC: 0 AN: 6

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

African (AFR) AF: 0.0335 AC: 1392 AN: 41570

American (AMR) AF: 0.0687 AC: 1051 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3472

East Asian (EAS) AF: 0.134 AC: 689 AN: 5144

South Asian (SAS) AF: 0.143 AC: 692 AN: 4830

European-Finnish (FIN) AF: 0.0531 AC: 563 AN: 10612

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0851 AC: 5790 AN: 68026

Other (OTH) AF: 0.0705 AC: 149 AN: 2112

Alfa AF: 0.0758 Hom.: 61

Bravo AF: 0.0693

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.93
PromoterAI		-0.057	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: rs3737898; hg19: chr1-63833450;