Variant chr13-52024711-TAAG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5

The NM_001004127.3(ALG11):c.986_988del(p.Lys329del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ALG11
NM_001004127.3 inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:2U:1

Conservation

PhyloP100: 4.71

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:

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_001004127.3. Strenght limited to Supporting due to length of the change: 1aa.

PP5

Variant 13-52024711-TAAG-T is Pathogenic according to our data. Variant chr13-52024711-TAAG-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 420418.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ALG11	NM_001004127.3 linkuse as main transcript	c.986_988del	p.Lys329del	inframe_deletion	3/4	ENST00000521508.2
UTP14C	NM_021645.6 linkuse as main transcript	c.-708_-706del		5_prime_UTR_variant	1/2	ENST00000521776.2
ALG11	NR_036571.3 linkuse as main transcript	n.66-3603_66-3601del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG11	ENST00000521508.2 linkuse as main transcript	c.986_988del	p.Lys329del	inframe_deletion	3/4	1	NM_001004127.3	P4
UTP14C	ENST00000521776.2 linkuse as main transcript	c.-708_-706del		5_prime_UTR_variant	1/2	1	NM_021645.6	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461876

Hom.:

AF XY:

0.00

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:2Uncertain:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Pathogenic:1Uncertain:1

Likely pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Jan 26, 2016	The c.986_988delAGA variant has not been reported previously as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. This variant causes an inframe deletion of a single amino acid residue,denoted p.Lys329del. This deletion occurs at a region that is not conserved; however, this variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.986_988delAGA variant is a strong candidate for a pathogenic variant. -
Uncertain significance, criteria provided, single submitter	clinical testing	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	Aug 29, 2022	PM4, PM2, PM3_Supporting -

ALG11-congenital disorder of glycosylation

Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Genomics England Pilot Project, Genomics England

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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