NM_001008216.2(GALE):c.770A>G (p.Lys257Arg) AND not specified

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Feb 21, 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:: RCV000609606.11

Allele description [Variation Report for NM_001008216.2(GALE):c.770A>G (p.Lys257Arg)]

NM_001008216.2(GALE):c.770A>G (p.Lys257Arg)

Gene:

GALE:UDP-galactose-4-epimerase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.11

Genomic location:

Preferred name:

NM_001008216.2(GALE):c.770A>G (p.Lys257Arg)

HGVS:

NC_000001.11:g.23796722T>C
NG_007068.1:g.9083A>G
NM_000403.4:c.770A>G
NM_001008216.2:c.770A>GMANE SELECT
NM_001127621.2:c.770A>G
NP_000394.2:p.Lys257Arg
NP_000394.2:p.Lys257Arg
NP_001008217.1:p.Lys257Arg
NP_001121093.1:p.Lys257Arg
NC_000001.10:g.24123212T>C
NM_000403.3:c.770A>G
NM_001127621.2:c.770A>G
Q14376:p.Lys257Arg

Protein change:

K257R; LYS257ARG

Links:

UniProtKB: Q14376#VAR_002544; OMIM: 606953.0005; dbSNP: rs28940884

Molecular consequence:

NM_000403.4:c.770A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001008216.2:c.770A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127621.2:c.770A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000730667	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely benign (Feb 1, 2018)	germline	clinical testing	Citation Link,
SCV002500159	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Mar 7, 2022)	germline	clinical testing	Citation Link,
SCV004847446	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Benign (Feb 21, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000730667

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely benign
(Feb 1, 2018)

germline

clinical testing

Citation Link,

SCV002500159

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Mar 7, 2022)

germline

clinical testing

Citation Link,

SCV004847446

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Benign
(Feb 21, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000730667.1

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002500159.1

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

Description

Variant summary: GALE c.770A>G (p.Lys257Arg) results in a conservative amino acid change in the encoded protein sequence. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 248990 control chromosomes, predominantly at a frequency of 0.019 within the African or African-American subpopulation in the gnomAD database, including 5 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 17 fold of the estimated maximal expected allele frequency for a pathogenic variant in GALE causing UDPglucose-4-Epimerase Deficiency phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and a majority consensus as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

#	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

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847446.1

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

Description

The p.Lys257Arg variant in GALE is classified as likely benign because it has been identified in 1.9% (1474/75008) of African chromosomes, including 24 total homozygotes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BS1.

#	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: Jul 6, 2026

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