13-52024663-G-A

Position:

chr13-52024663-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001004127.3(ALG11):c.933G>A(p.Pro311Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 1,613,952 control chromosomes in the GnomAD database, including 1,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 132 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1843 hom. )

Consequence

ALG11
NM_001004127.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.95

Variant links:

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 links:

ALG11 (HGNC:):

ALG11 links:

UTP14C (HGNC:20321): (UTP14C small subunit processome component) Predicted to be involved in several processes, including meiotic cell cycle; rRNA processing; and spermatogenesis. Located in cytosol and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

UTP14C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 13-52024663-G-A is Benign according to our data. Variant chr13-52024663-G-A is described in ClinVar as [Benign]. Clinvar id is 312413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.95 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALG11	NM_001004127.3 linkuse as main transcript	c.933G>A	p.Pro311Pro	synonymous_variant	3/4	ENST00000521508.2	NP_001004127.2	Q2TAA5
ALG11	NR_036571.3 linkuse as main transcript	n.66-3656G>A		intron_variant
UTP14C	NM_021645.6 linkuse as main transcript	c.-761G>A		upstream_gene_variant		ENST00000521776.2	NP_067677.4	Q5TAP6A0A024RDV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG11	ENST00000521508.2 linkuse as main transcript	c.933G>A	p.Pro311Pro	synonymous_variant	3/4	1	NM_001004127.3	ENSP00000430236.1		Q2TAA5
UTP14C	ENST00000521776.2 linkuse as main transcript	c.-761G>A		upstream_gene_variant		1	NM_021645.6	ENSP00000428619.1		Q5TAP6

Frequencies

GnomAD3 genomes

AF:

0.0346

AC:

5265

AN:

152148

Hom.:

130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0288

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.00961

Gnomad SAS

AF:

0.0899

Gnomad FIN

AF:

0.0284

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0469

Gnomad OTH

AF:

0.0417

GnomAD3 exomes

AF:

0.0425

AC:

10655

AN:

250920

Hom.:

321

AF XY:

0.0473

AC XY:

6414

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.0212

Gnomad ASJ exome

AF:

0.0531

Gnomad EAS exome

AF:

0.00877

Gnomad SAS exome

AF:

0.0881

Gnomad FIN exome

AF:

0.0317

Gnomad NFE exome

AF:

0.0475

Gnomad OTH exome

AF:

0.0448

GnomAD4 exome

AF:

0.0462

AC:

67528

AN:

1461686

Hom.:

1843

Cov.:

AF XY:

0.0479

AC XY:

34845

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.0119

Gnomad4 AMR exome

AF:

0.0210

Gnomad4 ASJ exome

AF:

0.0512

Gnomad4 EAS exome

AF:

0.00857

Gnomad4 SAS exome

AF:

0.0900

Gnomad4 FIN exome

AF:

0.0310

Gnomad4 NFE exome

AF:

0.0467

Gnomad4 OTH exome

AF:

0.0458

GnomAD4 genome

AF:

0.0346

AC:

5269

AN:

152266

Hom.:

132

Cov.:

AF XY:

0.0347

AC XY:

2581

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0131

Gnomad4 AMR

AF:

0.0287

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.00963

Gnomad4 SAS

AF:

0.0900

Gnomad4 FIN

AF:

0.0284

Gnomad4 NFE

AF:

0.0469

Gnomad4 OTH

AF:

0.0450

Alfa

AF:

0.0417

Hom.:

Bravo

AF:

0.0315

Asia WGS

AF:

0.0640

AC:

221

AN:

3478

EpiCase

AF:

0.0505

EpiControl

AF:

0.0518

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

ALG11-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 22, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

ALG11-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.70

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over