NM_005787.6(ALG3):c.521A>G (p.Asn174Ser) AND ALG3-congenital disorder of glycosylation

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Feb 23, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001543411.2

Allele description [Variation Report for NM_005787.6(ALG3):c.521A>G (p.Asn174Ser)]

NM_005787.6(ALG3):c.521A>G (p.Asn174Ser)

Gene:

ALG3:ALG3 alpha-1,3- mannosyltransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q27.1

Genomic location:

Preferred name:

NM_005787.6(ALG3):c.521A>G (p.Asn174Ser)

HGVS:

NC_000003.12:g.184245282T>C
NG_008924.2:g.9231A>G
NM_001006941.2:c.377A>G
NM_005787.6:c.521A>GMANE SELECT
NP_001006942.1:p.Asn126Ser
NP_005778.1:p.Asn174Ser
NC_000003.11:g.183963070T>C
NR_024533.1:n.452A>G
NR_024534.1:n.515A>G

Protein change:

N126S

Links:

dbSNP: rs1719068613

NCBI 1000 Genomes Browser:

rs1719068613

Molecular consequence:

NM_001006941.2:c.377A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005787.6:c.521A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_024533.1:n.452A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_024534.1:n.515A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: ALG3-congenital disorder of glycosylation
Synonyms:: CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Id; CDG Id; CARBOHYDRATE-DEFICIENT GLYCOPROTEIN SYNDROME, TYPE IV; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010998; MedGen: C1832736; Orphanet: 79321; OMIM: 601110

Recent activity

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uncharacterized protein LOC112031151 [Quercus suber]
uncharacterized protein LOC112031151 [Quercus suber]
gi|1344071628|ref|XP_023919605.1|

Protein
calcium-dependent protein kinase SK5-like [Cucurbita maxima]
calcium-dependent protein kinase SK5-like [Cucurbita maxima]
gi|1281057143|ref|XP_022970875.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001761971	University of Washington Center for Mendelian Genomics, University of Washington	no assertion criteria provided	Likely pathogenic	inherited	research	PubMed (1) [See all records that cite this PMID]
SCV003842041	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33583022, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001761971

University of Washington Center for Mendelian Genomics, University of Washington

no assertion criteria provided

Likely pathogenic

inherited

research

PubMed (1)
[See all records that cite this PMID]

SCV003842041

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 23, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Expanding the phenotype, genotype and biochemical knowledge of ALG3-CDG.

Alsharhan H, Ng BG, Daniel EJP, Friedman J, Pivnick EK, Al-Hashem A, Faqeih EA, Liu P, Engelhardt NM, Keller KN, Chen J, Mazzeo PA; University of Washington Center for Mendelian Genomics (UW-CMG)., Rosenfeld JA, Bamshad MJ, Nickerson DA, Raymond KM, Freeze HH, He M, Edmondson AC, Lam C.

J Inherit Metab Dis. 2021 Jul;44(4):987-1000. doi: 10.1002/jimd.12367. Epub 2021 Mar 1.

PubMed [citation]

PMID:: 33583022
PMCID:: PMC8282734

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From University of Washington Center for Mendelian Genomics, University of Washington, SCV001761971.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV003842041.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.85; 3Cnet: 0.83). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with ALG3 related disorder (ClinVar ID: VCV001184851 / PMID: 33583022). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 33583022). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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