rs111871296

Variant names:

• chr13-52012616-G-A
• rs111871296
• NM_001004127.3:c.44+154G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-52012616-G-A
• chr13-52012616-G-C
• chr13-52012616-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001004127.3(ALG11):​c.44+154G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 152,110 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.042 (166 hom., cov: 33)
• Consequence: ALG11 NM_001004127.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.698
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 13-52012616-G-A is Benign according to our data. Variant chr13-52012616-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1143193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0838 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.44+154G>A		intron	N/A	NP_001004127.2	Q2TAA5
	ALG11	NR_036571.3		n.65+154G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG11	ENST00000521508.2	TSL:1 MANE Select	c.44+154G>A		intron	N/A	ENSP00000430236.1	Q2TAA5
	ALG11	ENST00000649340.2		c.44+154G>A		intron	N/A	ENSP00000497184.2	A0A3B3IS90
	ALG11	ENST00000681053.1		c.44+154G>A		intron	N/A	ENSP00000505307.1	A0A7P0T8Y4

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6430 AN: 151992 Hom.: 163 Cov.: 33

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.00925

Gnomad SAS AF: 0.0908

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0469

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

GnomAD4 genome AF: 0.0423 AC: 6438 AN: 152110 Hom.: 166 Cov.: 33 AF XY: 0.0419 AC XY: 3116 AN XY: 74366

African (AFR) AF: 0.0403 AC: 1672 AN: 41502

American (AMR) AF: 0.0308 AC: 471 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3468

East Asian (EAS) AF: 0.00927 AC: 48 AN: 5178

South Asian (SAS) AF: 0.0909 AC: 437 AN: 4810

European-Finnish (FIN) AF: 0.0283 AC: 300 AN: 10584

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

European-Non Finnish (NFE) AF: 0.0469 AC: 3186 AN: 67966

Other (OTH) AF: 0.0502 AC: 106 AN: 2112

Alfa AF: 0.0406 Hom.: 189

Bravo AF: 0.0404

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ALG11-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.53
PhyloP100		0.70
PromoterAI		-0.016	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: rs111871296; hg19: chr13-52586752;