NM_013339.4:c.-136C>G

Variant names:

• chr1-63370842-C-G
• rs34542411
• NM_013339.4:c.-136C>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.-136C>G 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 0.196 in 714,454 control chromosomes in the GnomAD database, including 14,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3157 hom., cov: 32)
  • Exomes 𝑓: 0.19 (11127 hom.)
• Consequence: ALG6 NM_013339.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0690
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-63370842-C-G is Benign according to our data. Variant chr1-63370842-C-G is described in ClinVar as Benign. ClinVar VariationId is 297843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 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.-136C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	NP_037471.2
	ALG6	NM_013339.4	MANE Select	c.-136C>G		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.-136C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	ENSP00000263440.5	Q9Y672
	ALG6	ENST00000263440.6	TSL:5 MANE Select	c.-136C>G		5_prime_UTR	Exon 2 of 15	ENSP00000263440.5	Q9Y672
	ALG6	ENST00000948329.1		c.-136C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	ENSP00000618388.1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30456 AN: 151798 Hom.: 3152 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.195 AC: 109427 AN: 562538 Hom.: 11127 Cov.: 6 AF XY: 0.195 AC XY: 59531 AN XY: 304740

African (AFR) AF: 0.236 AC: 3575 AN: 15146

American (AMR) AF: 0.199 AC: 6294 AN: 31616

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 5695 AN: 18552

East Asian (EAS) AF: 0.205 AC: 6754 AN: 32918

South Asian (SAS) AF: 0.206 AC: 12305 AN: 59832

European-Finnish (FIN) AF: 0.147 AC: 6987 AN: 47534

Middle Eastern (MID) AF: 0.286 AC: 1123 AN: 3928

European-Non Finnish (NFE) AF: 0.187 AC: 60490 AN: 322678

Other (OTH) AF: 0.205 AC: 6204 AN: 30334

GnomAD4 genome AF: 0.201 AC: 30489 AN: 151916 Hom.: 3157 Cov.: 32 AF XY: 0.198 AC XY: 14700 AN XY: 74252

African (AFR) AF: 0.235 AC: 9733 AN: 41410

American (AMR) AF: 0.196 AC: 2984 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3468

East Asian (EAS) AF: 0.185 AC: 954 AN: 5160

South Asian (SAS) AF: 0.196 AC: 944 AN: 4814

European-Finnish (FIN) AF: 0.142 AC: 1496 AN: 10552

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12613 AN: 67960

Other (OTH) AF: 0.217 AC: 457 AN: 2108

Alfa AF: 0.187 Hom.: 376

Bravo AF: 0.208

Asia WGS AF: 0.183 AC: 633 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ALG6-congenital disorder of glycosylation 1C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.4
DANN	Benign	0.76
PhyloP100		-0.069
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	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: rs34542411; hg19: chr1-63836513; COSMIC: COSV54763906;