rs61958801

Variant names:

• chr13-52018582-G-C
• rs61958801
• NM_001004127.3:c.45-331G>C

Variant summary

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

The NM_001004127.3(ALG11):​c.45-331G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 152,168 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.034 (129 hom., cov: 32)
• Consequence: ALG11 NM_001004127.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.457
• Publications: 0 publications found

Genes affected

ALG11 (HGNC:32456): (ALG11 alpha-1,2-mannosyltransferase) This gene encodes a GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase which is localized to the cytosolic side of the endoplasmic reticulum (ER) and catalyzes the transfer of the fourth and fifth mannose residue from GDP-mannose (GDP-Man) to Man3GlcNAc2-PP-dolichol and Man4GlcNAc2-PP-dolichol resulting in the production of Man5GlcNAc2-PP-dolichol. Mutations in this gene are associated with congenital disorder of glycosylation type Ip (CDGIP). This gene overlaps but is distinct from the UTP14, U3 small nucleolar ribonucleoprotein, homolog C (yeast) gene. A pseudogene of the GDP-Man:Man3GlcNAc2-PP-dolichol-alpha1,2-mannosyltransferase has been identified on chromosome 19. [provided by RefSeq, Aug 2010]

ALG11 Gene-Disease associations (from GenCC):

• ALG11-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 13-52018582-G-C is Benign according to our data. Variant chr13-52018582-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1218191.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004127.3. 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
	ALG11	NM_001004127.3	MANE Select	c.45-331G>C		intron	N/A	NP_001004127.2	Q2TAA5
	ALG11	NR_036571.3		n.65+6120G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG11	ENST00000521508.2	TSL:1 MANE Select	c.45-331G>C		intron	N/A	ENSP00000430236.1	Q2TAA5
	ALG11	ENST00000649340.2		c.45-331G>C		intron	N/A	ENSP00000497184.2	A0A3B3IS90
	ALG11	ENST00000681053.1		c.45-5424G>C		intron	N/A	ENSP00000505307.1	A0A7P0T8Y4

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 5209 AN: 152050 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.00963

Gnomad SAS AF: 0.0905

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0466

Gnomad OTH AF: 0.0413

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

GnomAD4 genome AF: 0.0343 AC: 5213 AN: 152168 Hom.: 129 Cov.: 32 AF XY: 0.0344 AC XY: 2558 AN XY: 74390

African (AFR) AF: 0.0125 AC: 517 AN: 41510

American (AMR) AF: 0.0284 AC: 435 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0521 AC: 181 AN: 3472

East Asian (EAS) AF: 0.00965 AC: 50 AN: 5182

South Asian (SAS) AF: 0.0906 AC: 436 AN: 4814

European-Finnish (FIN) AF: 0.0283 AC: 299 AN: 10584

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0465 AC: 3165 AN: 68004

Other (OTH) AF: 0.0446 AC: 94 AN: 2106

Alfa AF: 0.0397 Hom.: 18

Bravo AF: 0.0313

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.87
CADD	Benign	0.22
DANN	Benign	0.64
PhyloP100		-0.46
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: rs61958801; hg19: chr13-52592718;