NM_000503.6(EYA1):c.1246G>A (p.Ala416Thr) AND Melnick-Fraser syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 18, 2023
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:: RCV003593497.2

Allele description [Variation Report for NM_000503.6(EYA1):c.1246G>A (p.Ala416Thr)]

NM_000503.6(EYA1):c.1246G>A (p.Ala416Thr)

Gene:

EYA1:EYA transcriptional coactivator and phosphatase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q13.3

Genomic location:

Preferred name:

NM_000503.6(EYA1):c.1246G>A (p.Ala416Thr)

HGVS:

NC_000008.11:g.71216806C>T
NG_011735.3:g.336325G>A
NG_011735.4:g.336288G>A
NM_000503.6:c.1246G>AMANE SELECT
NM_001288574.2:c.1228G>A
NM_001288575.2:c.880G>A
NM_001370333.1:c.1333G>A
NM_001370334.1:c.1246G>A
NM_001370335.1:c.1246G>A
NM_001370336.1:c.1225G>A
NM_001411797.1:c.1147G>A
NM_172058.4:c.1246G>A
NM_172059.5:c.1228G>A
NM_172060.4:c.1147G>A
NP_000494.2:p.Ala416Thr
NP_001275503.1:p.Ala410Thr
NP_001275504.1:p.Ala294Thr
NP_001357262.1:p.Ala445Thr
NP_001357263.1:p.Ala416Thr
NP_001357264.1:p.Ala416Thr
NP_001357265.1:p.Ala409Thr
NP_001398726.1:p.Ala383Thr
NP_742055.1:p.Ala416Thr
NP_742056.2:p.Ala410Thr
NP_742057.1:p.Ala383Thr
NC_000008.10:g.72129041C>T

Protein change:

A294T

Molecular consequence:

NM_000503.6:c.1246G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288574.2:c.1228G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288575.2:c.880G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370333.1:c.1333G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370334.1:c.1246G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370335.1:c.1246G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370336.1:c.1225G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001411797.1:c.1147G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172058.4:c.1246G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172059.5:c.1228G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_172060.4:c.1147G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Melnick-Fraser syndrome (BOR)
Synonyms:: Branchio-oto-renal syndrome; Branchiootorenal syndrome
Identifiers:: MONDO: MONDO:0007029; MedGen: C0265234; OMIM: PS113650

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
SCV004368627	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 18, 2023)	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

SCV004368627

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 18, 2023)

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004368627.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 not expected to disrupt EYA1 protein function. This variant has not been reported in the literature in individuals affected with EYA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 416 of the EYA1 protein (p.Ala416Thr).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine