rs1016079273

Variant names:

• chr1-63370858-C-T
• rs1016079273
• NM_013339.4:c.-120C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-63370858-C-T
• chr1-63370858-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_013339.4(ALG6):​c.-120C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 759,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: ALG6 NM_013339.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.48
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	NP_037471.2
	ALG6	NM_013339.4	MANE Select	c.-120C>T		5_prime_UTR	Exon 2 of 15	NP_037471.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG6	ENST00000263440.6	TSL:5 MANE Select	c.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	ENSP00000263440.5	Q9Y672
	ALG6	ENST00000263440.6	TSL:5 MANE Select	c.-120C>T		5_prime_UTR	Exon 2 of 15	ENSP00000263440.5	Q9Y672
	ALG6	ENST00000948329.1		c.-120C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	ENSP00000618388.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151982 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000444 AC: 27 AN: 607562 Hom.: 0 Cov.: 7 AF XY: 0.0000425 AC XY: 14 AN XY: 329692

African (AFR) AF: 0.00 AC: 0 AN: 16308

American (AMR) AF: 0.00 AC: 0 AN: 36306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19766

East Asian (EAS) AF: 0.00 AC: 0 AN: 34672

South Asian (SAS) AF: 0.0000628 AC: 4 AN: 63720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4072

European-Non Finnish (NFE) AF: 0.0000629 AC: 22 AN: 349912

Other (OTH) AF: 0.0000312 AC: 1 AN: 32084

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 151982 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74226

African (AFR) AF: 0.00 AC: 0 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15262

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	ALG6-congenital disorder of glycosylation 1C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.3
DANN	Benign	0.83
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1016079273; hg19: chr1-63836529; COSMIC: COSV104554353;