NM_000155.4(GALT):c.590A>G (p.Asp197Gly) AND Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: May 2, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000671944.5

Allele description [Variation Report for NM_000155.4(GALT):c.590A>G (p.Asp197Gly)]

NM_000155.4(GALT):c.590A>G (p.Asp197Gly)

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.590A>G (p.Asp197Gly)

HGVS:

NC_000009.12:g.34648359A>G
NG_009029.2:g.6771A>G
NG_028966.1:g.1175A>G
NM_000155.4:c.590A>GMANE SELECT
NM_001258332.2:c.263A>G
NP_000146.2:p.Asp197Gly
NP_001245261.1:p.Asp88Gly
NC_000009.11:g.34648356A>G
NM_000155.3:c.590A>G

Protein change:

D197G

Links:

dbSNP: rs1554709359

NCBI 1000 Genomes Browser:

rs1554709359

Molecular consequence:

NM_000155.4:c.590A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258332.2:c.263A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase
Synonyms:: GALACTOSE-1-PHOSPHATE URIDYLYLTRANSFERASE DEFICIENCY; Galactose-1-phosphate uridyltransferase deficiency; Transferase Deficiency Galactosemia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009258; MedGen: C0268151; Orphanet: 352; Orphanet: 79239; OMIM: 230400

Recent activity

Clear Turn Off Turn On

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
SCV000796988	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jan 16, 2018)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23690308, 28065439, 22743281 Citation Link,
SCV002247896	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 2, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22743281, 28065439, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000796988

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Jan 16, 2018)

unknown

clinical testing

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

Citation Link,

SCV002247896

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 2, 2023)

germline

clinical testing

PubMed (3)
[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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Modifiers of ovarian function in girls and women with classic galactosemia.

Spencer JB, Badik JR, Ryan EL, Gleason TJ, Broadaway KA, Epstein MP, Fridovich-Keil JL.

J Clin Endocrinol Metab. 2013 Jul;98(7):E1257-65. doi: 10.1210/jc.2013-1374. Epub 2013 May 20.

PubMed [citation]

PMID:: 23690308
PMCID:: PMC3701263

N- and O-linked glycosylation of total plasma glycoproteins in galactosemia.

Liu Y, Xia B, Gleason TJ, Castañeda U, He M, Berry GT, Fridovich-Keil JL.

Mol Genet Metab. 2012 Aug;106(4):442-54. doi: 10.1016/j.ymgme.2012.05.025. Epub 2012 Jun 12.

PubMed [citation]

PMID:: 22743281
PMCID:: PMC3426456

See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000796988.1

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

From Invitae, SCV002247896.3

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GALT protein function. ClinVar contains an entry for this variant (Variation ID: 556007). This missense change has been observed in individual(s) with clinical features of galactosemia (PMID: 22743281, 28065439). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 197 of the GALT protein (p.Asp197Gly).

#	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: Feb 20, 2024

ClinVar

Relating variation to medicine