dbSNP rs141089354: ALG11:p.Asn397Lys (chr13-52024921-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001004127.3(ALG11):c.1191C>A(p.Asn397Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ALG11
NM_001004127.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0870

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:

Genome browser will be placed here

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;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.919

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG11	NM_001004127.3 link	c.1191C>A	p.Asn397Lys	missense_variant	Exon 3 of 4	ENST00000521508.2	NP_001004127.2	Q2TAA5
UTP14C	NM_021645.6 link	c.-503C>A		5_prime_UTR_variant	Exon 1 of 2	ENST00000521776.2	NP_067677.4	Q5TAP6A0A024RDV0
ALG11	NR_036571.3 link	n.66-3398C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG11	ENST00000521508.2 link	c.1191C>A	p.Asn397Lys	missense_variant	Exon 3 of 4	1	NM_001004127.3	ENSP00000430236.1		Q2TAA5
UTP14C	ENST00000521776 link	c.-503C>A		5_prime_UTR_variant	Exon 1 of 2	1	NM_021645.6	ENSP00000428619.1		Q5TAP6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

244060

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457820

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725314

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.67

Eigen

Benign

-0.056

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.47

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.20

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.6

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.94

MutPred

0.64

Gain of catalytic residue at F400 (P = 0);

MVP

0.81

MPC

0.33

ClinPred

0.98

GERP RS

-2.0

Varity_R

0.88

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over