13-52012786-T-C

Position:

• chr13-52012786-T-C

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+324T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 152,240 control chromosomes in the GnomAD database, including 190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.043 (190 hom., cov: 32)
• Consequence: ALG11 NM_001004127.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.340

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=-0.8).
• BP6: Variant 13-52012786-T-C is Benign according to our data. Variant chr13-52012786-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 487323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-52012786-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG11	NM_001004127.3	c.44+324T>C		intron_variant		ENST00000521508.2	NP_001004127.2
ALG11	NR_036571.3	n.65+324T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG11	ENST00000521508.2	c.44+324T>C		intron_variant		1	NM_001004127.3	ENSP00000430236	P4

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6593 AN: 152122 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0516

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.0420

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

GnomAD4 genome AF: 0.0433 AC: 6592 AN: 152240 Hom.: 190 Cov.: 32 AF XY: 0.0410 AC XY: 3050 AN XY: 74438

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.0266

Gnomad4 ASJ AF: 0.0640

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0514

Gnomad4 FIN AF: 0.0348

Gnomad4 NFE AF: 0.0693

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0623 Hom.: 46

Bravo AF: 0.0405

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

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

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs77505745; hg19: chr13-52586922;