NM_000155.4(GALT):c.265T>G (p.Tyr89Asp) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 6, 2022
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:: RCV000482282.13

Allele description [Variation Report for NM_000155.4(GALT):c.265T>G (p.Tyr89Asp)]

NM_000155.4(GALT):c.265T>G (p.Tyr89Asp)

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.265T>G (p.Tyr89Asp)

Other names:

p.Tyr89Asp

HGVS:

NC_000009.12:g.34647504T>G
NG_009029.2:g.5916T>G
NG_028966.1:g.320T>G
NM_000155.3:c.265T>G
NM_000155.4:c.265T>GMANE SELECT
NM_001258332.2:c.50+246T>G
NP_000146.2:p.Tyr89Asp
NC_000009.11:g.34647501T>G
NM_000155.2:c.265T>G
NM_000155.4:c.265T>G

Links:

dbSNP: rs111033666

NCBI 1000 Genomes Browser:

rs111033666

Molecular consequence:

NM_001258332.2:c.50+246T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000155.4:c.265T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000567775	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Aug 26, 2015)	germline	clinical testing	Citation Link,
SCV000854788	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Nov 28, 2017)	germline	clinical testing	Citation Link,
SCV004226583	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 6, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27005423, 35134457, 35677809, 25741868 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000567775

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Aug 26, 2015)

germline

clinical testing

Citation Link,

SCV000854788

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Nov 28, 2017)

germline

clinical testing

Citation Link,

SCV004226583

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 6, 2022)

germline

clinical testing

PubMed (4)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	6	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular basis of classic galactosemia from the structure of human galactose 1-phosphate uridylyltransferase.

McCorvie TJ, Kopec J, Pey AL, Fitzpatrick F, Patel D, Chalk R, Shrestha L, Yue WW.

Hum Mol Genet. 2016 Jun 1;25(11):2234-2244. Epub 2016 Mar 22.

PubMed [citation]

PMID:: 27005423
PMCID:: PMC5081055

MotSASi: Functional short linear motifs (SLiMs) prediction based on genomic single nucleotide variants and structural data.

Martín M, Brunello FG, Modenutti CP, Nicola JP, Marti MA.

Biochimie. 2022 Jun;197:59-73. doi: 10.1016/j.biochi.2022.02.002. Epub 2022 Feb 5.

PubMed [citation]

PMID:: 35134457

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000567775.4

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

Description

The Y89D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (Y89H, N86D and F95L) have been reported in the Human Gene Mutation Database in association with galactosemia (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, we interpret Y89D to be a pathogenic variant.

#	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

From Eurofins Ntd Llc (ga), SCV000854788.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	not provided

#	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		4	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV004226583.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (4)

Description

PP3, PP4, PM2, PS4_moderate

#	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		2	not provided	not provided	not provided

Last Updated: Sep 8, 2024

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