Genetic Variant ALG5:p.Ala19Thr (chr13-36999246-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_013338.5(ALG5):c.55G>A(p.Ala19Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A19S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ALG5
NM_013338.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.829

Publications

0 publications found

Variant links:

Genes affected

ALG5 (HGNC:20266): (ALG5 dolichyl-phosphate beta-glucosyltransferase) This gene encodes a member of the glycosyltransferase 2 family. The encoded protein participates in glucosylation of the oligomannose core in N-linked glycosylation of proteins. The addition of glucose residues to the oligomannose core is necessary to ensure substrate recognition, and therefore, effectual transfer of the oligomannose core to the nascent glycoproteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

ALG5 links:

EXOSC8 (HGNC:17035): (exosome component 8) This gene encodes a 3'-5' exoribonuclease that specifically interacts with mRNAs containing AU-rich elements. The encoded protein is part of the exosome complex that is important for the degradation of numerous RNA species. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Mar 2009]

EXOSC8 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia, type 1C
Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
pontocerebellar hypoplasia type 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EXOSC8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2865519).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013338.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG5	NM_013338.5	MANE Select	c.55G>A	p.Ala19Thr	missense	Exon 1 of 10	NP_037470.1	Q9Y673-1
	ALG5	NM_001142364.1		c.55G>A	p.Ala19Thr	missense	Exon 1 of 9	NP_001135836.1	Q9Y673-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG5	ENST00000239891.4	TSL:1 MANE Select	c.55G>A	p.Ala19Thr	missense	Exon 1 of 10	ENSP00000239891.3	Q9Y673-1
ALG5	ENST00000857206.1		c.55G>A	p.Ala19Thr	missense	Exon 1 of 11	ENSP00000527265.1
ALG5	ENST00000857208.1		c.55G>A	p.Ala19Thr	missense	Exon 1 of 10	ENSP00000527267.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1428422

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710418

African (AFR)

AF:

0.00

AC:

AN:

30368

American (AMR)

AF:

0.00

AC:

AN:

39946

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25248

East Asian (EAS)

AF:

0.00

AC:

AN:

35058

South Asian (SAS)

AF:

0.00

AC:

AN:

82792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098326

Other (OTH)

AF:

0.00

AC:

AN:

59012

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.22

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.30

MutationAssessor

Uncertain

2.4

PhyloP100

0.83

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.41

REVEL

Uncertain

0.29

Sift

Benign

0.52

Sift4G

Benign

0.44

Polyphen

0.83

Vest4

0.26

MutPred

0.41

Gain of catalytic residue at S24 (P = 0.0011)

MVP

0.89

MPC

0.40

ClinPred

0.41

GERP RS

5.2

PromoterAI

0.041

Neutral

(source)

Varity_R

0.12

gMVP

0.73

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over