13-52012616-G-A

Position:

• chr13-52012616-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG11	NM_001004127.3	c.44+154G>A		intron_variant		ENST00000521508.2	NP_001004127.2
ALG11	NR_036571.3	n.65+154G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG11	ENST00000521508.2	c.44+154G>A		intron_variant		1	NM_001004127.3	ENSP00000430236	P4

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

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.0308

Gnomad4 ASJ AF: 0.0522

Gnomad4 EAS AF: 0.00927

Gnomad4 SAS AF: 0.0909

Gnomad4 FIN AF: 0.0283

Gnomad4 NFE AF: 0.0469

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0183 Hom.: 5

Bravo AF: 0.0404

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

ALG11-congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs111871296; hg19: chr13-52586752;