NM_000512.5(GALNS):c.824T>C (p.Leu275Pro) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 4, 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:: RCV003399148.1

Allele description [Variation Report for NM_000512.5(GALNS):c.824T>C (p.Leu275Pro)]

NM_000512.5(GALNS):c.824T>C (p.Leu275Pro)

Gene:

GALNS:galactosamine (N-acetyl)-6-sulfatase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.3

Genomic location:

Preferred name:

NM_000512.5(GALNS):c.824T>C (p.Leu275Pro)

HGVS:

NC_000016.10:g.88835287A>G
NG_008667.1:g.26680T>C
NM_000512.5:c.824T>CMANE SELECT
NM_001323543.2:c.269T>C
NM_001323544.2:c.842T>C
NP_000503.1:p.Leu275Pro
NP_001310472.1:p.Leu90Pro
NP_001310473.1:p.Leu281Pro
NC_000016.9:g.88901695A>G

Protein change:

L275P

Links:

dbSNP: rs2143001162

NCBI 1000 Genomes Browser:

rs2143001162

Molecular consequence:

NM_000512.5:c.824T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001323543.2:c.269T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001323544.2:c.842T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Drought-responsive family protein [Arabidopsis thaliana]
Drought-responsive family protein [Arabidopsis thaliana]
gi|15240426|ref|NP_198051.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004122460	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Oct 4, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 34387910, 25545067, 32216080 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004122460

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Oct 4, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome): A review and classification of GALNS gene variants and reporting of 68 novel variants.

Zanetti A, D'Avanzo F, AlSayed M, Brusius-Facchin AC, Chien YH, Giugliani R, Izzo E, Kasper DC, Lin HY, Lin SP, Pollard L, Singh A, Tonin R, Wood T, Morrone A, Tomanin R.

Hum Mutat. 2021 Nov;42(11):1384-1398. doi: 10.1002/humu.24270. Epub 2021 Aug 23. Review.

PubMed [citation]

PMID:: 34387910
PMCID:: PMC9291100

Optimizing the molecular diagnosis of GALNS: novel methods to define and characterize Morquio-A syndrome-associated mutations.

Caciotti A, Tonin R, Rigoldi M, Ferri L, Catarzi S, Cavicchi C, Procopio E, Donati MA, Ficcadenti A, Fiumara A, Barone R, Garavelli L, Rocco MD, Filocamo M, Antuzzi D, Scarpa M, Mooney SD, Li B, Skouma A, Bianca S, Concolino D, Casalone R, et al.

Hum Mutat. 2015 Mar;36(3):357-68. doi: 10.1002/humu.22751.

PubMed [citation]

PMID:: 25545067

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004122460.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: GALNS c.824T>C (p.Leu275Pro) results in a non-conservative amino acid change located in the Sulfatase, N-terminal domain (IPR000917) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249496 control chromosomes (gnomAD). c.824T>C has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IVA (Morquio Syndrome A) (examples: Caciotti_2015 and Peretz_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 25545067, 32216080, 34387910). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine