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NM_004183.4(BEST1):c.28G>A (p.Ala10Thr) AND not provided

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Aug 19, 2022
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:
RCV000086118.9

Allele description [Variation Report for NM_004183.4(BEST1):c.28G>A (p.Ala10Thr)]

NM_004183.4(BEST1):c.28G>A (p.Ala10Thr)

Gene:
BEST1:bestrophin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q12.3
Genomic location:
Preferred name:
NM_004183.4(BEST1):c.28G>A (p.Ala10Thr)
HGVS:
  • NC_000011.10:g.61951834G>A
  • NG_009033.1:g.6951G>A
  • NM_001139443.2:c.-29+1407G>A
  • NM_001300786.2:c.-29+1407G>A
  • NM_001300787.2:c.-29+1407G>A
  • NM_001363592.1:c.28G>A
  • NM_004183.4:c.28G>AMANE SELECT
  • NP_001350521.1:p.Ala10Thr
  • NP_004174.1:p.Ala10Thr
  • NC_000011.9:g.61719306G>A
  • NM_004183.3:c.28G>A
  • NR_134580.2:n.141G>A
  • O76090:p.Ala10Thr
Protein change:
A10T
Links:
UniProtKB: O76090#VAR_000833; dbSNP: rs281865206
NCBI 1000 Genomes Browser:
rs281865206
Molecular consequence:
  • NM_001139443.2:c.-29+1407G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001300786.2:c.-29+1407G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001300787.2:c.-29+1407G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001363592.1:c.28G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004183.4:c.28G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_134580.2:n.141G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000118262Retina International
no classification provided
not providednot providednot provided

SCV001384887Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 19, 2022) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Description

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providednot providednot providednot providednot providednot provided1not providedliterature only

Citations

PubMed

The mutation spectrum of the bestrophin protein--functional implications.

Bakall B, Marknell T, Ingvast S, Koisti MJ, Sandgren O, Li W, Bergen AA, Andreasson S, Rosenberg T, Petrukhin K, Wadelius C.

Hum Genet. 1999 May;104(5):383-9.

PubMed [citation]
PMID:
10394929

Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best's disease).

Marquardt A, Stöhr H, Passmore LA, Krämer F, Rivera A, Weber BH.

Hum Mol Genet. 1998 Sep;7(9):1517-25.

PubMed [citation]
PMID:
9700209
See all PubMed Citations (6)

Details of each submission

From Retina International, SCV000118262.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providednot providednot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot provided1not providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001384887.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ala10 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been observed in individuals with BEST1-related conditions (PMID: 10394929), which suggests that this may be a clinically significant amino acid residue. 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 BEST1 protein function. ClinVar contains an entry for this variant (Variation ID: 99706). This missense change has been observed in individuals with autosomal dominant Best vitelliform macular dystrophy (PMID: 9700209, 10854112, 25082885, 25174897). It has also been observed to segregate with disease in related individuals. 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 10 of the BEST1 protein (p.Ala10Thr).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 28, 2024