rs61958802

Variant names:

• chr13-52024663-G-A
• rs61958802
• NM_001004127.3:c.933G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.95

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]

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]

ACMG classification

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 rank	MANE	Protein	UniProt
ALG11	NM_001004127.3	c.933G>A	p.Pro311Pro	synonymous_variant	Exon 3 of 4	ENST00000521508.2	NP_001004127.2
ALG11	NR_036571.3	n.66-3656G>A		intron_variant	Intron 1 of 1
UTP14C	NM_021645.6	c.-761G>A		upstream_gene_variant		ENST00000521776.2	NP_067677.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG11	ENST00000521508.2	c.933G>A	p.Pro311Pro	synonymous_variant	Exon 3 of 4	1	NM_001004127.3	ENSP00000430236.1
UTP14C	ENST00000521776.2	c.-761G>A		upstream_gene_variant		1	NM_021645.6	ENSP00000428619.1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5265 AN: 152148 Hom.: 130 Cov.: 32

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

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.: 32 AF XY: 0.0479 AC XY: 34845 AN XY: 727126

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.: 32 AF XY: 0.0347 AC XY: 2581 AN XY: 74432

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.: 81

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

Submissions by phenotype

ALG11-congenital disorder of glycosylation Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Dec 22, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

ALG11-related disorder Benign:1

May 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	12
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

Other links and lift over

dbSNP: rs61958802; hg19: chr13-52598799;