1-63367765-C-G

Variant names:

• chr1-63367765-C-G
• rs3737897
• NM_013339.4:c.-208+78C>G

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+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
• 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=-0.75).
• BP6: Variant 1-63367765-C-G is Benign according to our data. Variant chr1-63367765-C-G is described in ClinVar as Benign. ClinVar VariationId 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.

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+78C>G		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+78C>G		intron	N/A	ENSP00000263440.5	Q9Y672
	ALG6	ENST00000948329.1		c.-208+83C>G		intron	N/A	ENSP00000618388.1
	ALG6	ENST00000920026.1		c.-208+78C>G		intron	N/A	ENSP00000590085.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

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

European-Non Finnish (NFE) AF: 0.129 AC: 16 AN: 124

Other (OTH) AF: 0.125 AC: 1 AN: 8

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

African (AFR) AF: 0.125 AC: 5173 AN: 41530

American (AMR) AF: 0.0777 AC: 1189 AN: 15300

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

East Asian (EAS) AF: 0.152 AC: 784 AN: 5148

South Asian (SAS) AF: 0.162 AC: 782 AN: 4828

European-Finnish (FIN) AF: 0.0639 AC: 679 AN: 10622

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0857 AC: 5824 AN: 67992

Other (OTH) AF: 0.0978 AC: 207 AN: 2116

Alfa AF: 0.0425 Hom.: 40

Bravo AF: 0.0992

Asia WGS AF: 0.175 AC: 608 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	-0.75
CADD	Benign	6.1
DANN	Benign	0.79
PhyloP100		-1.3
PromoterAI		-0.064	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: rs3737897; hg19: chr1-63833436;