NM_000155.4(GALT):c.221T>C (p.Leu74Pro) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 20, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000723459.8

Allele description [Variation Report for NM_000155.4(GALT):c.221T>C (p.Leu74Pro)]

NM_000155.4(GALT):c.221T>C (p.Leu74Pro)

Genes:

LOC130001683:ATAC-STARR-seq lymphoblastoid active region 28314 [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.221T>C (p.Leu74Pro)

HGVS:

NC_000009.12:g.34647227T>C
NG_009029.2:g.5639T>C
NG_028966.1:g.43T>C
NM_000155.4:c.221T>CMANE SELECT
NM_001258332.2:c.19T>C
NP_000146.2:p.Leu74Pro
NP_001245261.1:p.Cys7Arg
NC_000009.11:g.34647224T>C
NM_000155.2:c.221T>C
NM_000155.3:c.221T>C
P07902:p.Leu74Pro

Protein change:

C7R; LEU74PRO

Links:

UniProtKB: P07902#VAR_002557; OMIM: 606999.0007; dbSNP: rs111033663

NCBI 1000 Genomes Browser:

rs111033663

Molecular consequence:

NM_000155.4:c.221T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001258332.2:c.19T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000700444	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Mar 30, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 1610789, 20008339, 23583749 Citation Link,
SCV004226582	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30718057, 25741868
SCV005079064	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 20, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000700444

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Mar 30, 2017)

germline

clinical testing

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

Citation Link,

SCV004226582

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 22, 2023)

germline

clinical testing

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

SCV005079064

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 20, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	4	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular characterization of two galactosemia mutations and one polymorphism: implications for structure-function analysis of human galactose-1-phosphate uridyltransferase.

Reichardt JK, Levy HL, Woo SL.

Biochemistry. 1992 Jun 23;31(24):5430-3.

PubMed [citation]

PMID:: 1610789

Analysis of galactosemia-linked mutations of GALT enzyme using a computational biology approach.

Facchiano A, Marabotti A.

Protein Eng Des Sel. 2010 Feb;23(2):103-13. doi: 10.1093/protein/gzp076. Epub 2009 Dec 11.

PubMed [citation]

PMID:: 20008339

See all PubMed Citations (5)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000700444.3

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

#	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		3	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV004226582.1

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

Description

PP3, PP4, PM2, PM3, PS3

#	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		1	not provided	not provided	not provided

From GeneDx, SCV005079064.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Functional studies resulted in no GALT enzyme activity when L74P was over-expressed in COS cells and yeast cells (PMID: 1610789, 23583749); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20008339, 1301925, 23583749, 1610789, 7887416, 23891399, 7671959, 10408771, 11261429)

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

Last Updated: Apr 13, 2025

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