NM_000155.4(GALT):c.404C>T (p.Ser135Leu) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 23, 2021
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:: RCV002512724.9

Allele description [Variation Report for NM_000155.4(GALT):c.404C>T (p.Ser135Leu)]

NM_000155.4(GALT):c.404C>T (p.Ser135Leu)

Gene:

GALT:galactose-1-phosphate uridylyltransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_000155.4(GALT):c.404C>T (p.Ser135Leu)

Other names:

c.404C>T; p.S135L:TCG>TTG; NM_000155.3(GALT):c.404C>T(p.Ser135Leu); NM_001258332.1(GALT):c.77C>T(p.Ser26Leu)

HGVS:

NC_000009.12:g.34647858C>T
NG_009029.2:g.6270C>T
NG_028966.1:g.674C>T
NM_000155.4:c.404C>TMANE SELECT
NM_001258332.2:c.77C>T
NP_000146.2:p.Ser135Leu
NP_000146.2:p.Ser135Leu
NP_001245261.1:p.Ser26Leu
NP_001245261.1:p.Ser26Leu
NC_000009.11:g.34647855C>T
NM_000155.1:c.404C>T
NM_000155.2:c.404C>T
NM_000155.3:c.404C>T
NM_000155.4:c.404C>T
NM_001258332.1:c.77C>T
P07902:p.Ser135Leu
c.404C>T (p.Ser135Leu)

Protein change:

S135L; SER135LEU

Links:

Genetic Testing Registry (GTR): GTR000500512; UniProtKB: P07902#VAR_002571; OMIM: 606999.0010; dbSNP: rs111033690

NCBI 1000 Genomes Browser:

rs111033690

Molecular consequence:

NM_000155.4:c.404C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258332.2:c.77C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003549281	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jun 23, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 7887417, 11152465, 12350230, 22944367, 25614870, 27176039, 31954591 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003549281

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jun 23, 2021)

germline

clinical testing

PubMed (7)
[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

Identification and functional analysis of three distinct mutations in the human galactose-1-phosphate uridyltransferase gene associated with galactosemia in a single family.

Fridovich-Keil JL, Langley SD, Mazur LA, Lennon JC, Dembure PP, Elsas JL 2nd.

Am J Hum Genet. 1995 Mar;56(3):640-6.

PubMed [citation]

PMID:: 7887417
PMCID:: PMC1801186

Relationship between genotype, activity, and galactose sensitivity in yeast expressing patient alleles of human galactose-1-phosphate uridylyltransferase.

Riehman K, Crews C, Fridovich-Keil JL.

J Biol Chem. 2001 Apr 6;276(14):10634-40. Epub 2001 Jan 4.

PubMed [citation]

PMID:: 11152465

See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV003549281.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The c.404C>T (p.S135L) alteration is located in exon 5 (coding exon 5) of the GALT gene. This alteration results from a C to T substitution at nucleotide position 404, causing the serine (S) at amino acid position 135 to be replaced by a leucine (L). Based on data from the Genome Aggregation Database (gnomAD) database, the GALT c.404C>T alteration was observed in 0.03% (94/282882) of total alleles studied, with a frequency of 0.35% (87/24960) in the African subpopulation. This mutation has been reported in multiple individuals in the homozygous and compound heterozygous states with galactosemia (Henderson, 2002; Boutron, 2012; Garcia, 2016; Welsink-Karssies, 2020). In yeast and E. coli, GALT activity was reduced compared to wild type (Fridovich-Keil, 1995; Riehman, 2001; Coelho, 2014). The p.S135L alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as 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: Nov 3, 2024

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